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Emerging evidence highlights the critical role of long non-coding RNAs (lncRNAs) in GBM pathogenesis, particularly through their interactions with RNA-binding proteins (RBPs). These interactions form complex regulatory networks that influence multiple GBM hallmarks, such as sustained proliferation, induction of angiogenesis, and immune evasion. Additionally, these interactions play a pivotal role in maintaining glioma stem-like cells, a subpopulation responsible for tumor recurrence and resistance to conventional therapies. Understanding the mechanistic basis of lncRNA-RBP interactions offers promising opportunities for therapeutic intervention. Targeting these networks could enable the development of novel and more effective treatment strategies. This review provides an in-depth analysis of the molecular mechanisms by which lncRNA-RBP complexes promote GBM development.<\/jats:p>","DOI":"10.3390\/cells15141251","type":"journal-article","created":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T07:28:27Z","timestamp":1783927707000},"page":"1251","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Hallmarks of Glioblastoma: Functional Interplay Between Long Non-Coding RNAs and RNA-Binding Proteins"],"prefix":"10.3390","volume":"15","author":[{"given":"Karlijn A.","family":"van de Langerijt","sequence":"first","affiliation":[{"name":"Harvey Cushing Neuro-Oncology Laboratories, Department of Neurosurgery, Brigham and Women\u2019s Hospital, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9973-4933","authenticated-orcid":false,"given":"Md Golam","family":"Kibria","sequence":"additional","affiliation":[{"name":"Harvey Cushing Neuro-Oncology Laboratories, Department of Neurosurgery, Brigham and Women\u2019s Hospital, Boston, MA 02115, USA"},{"name":"Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9461-2291","authenticated-orcid":false,"given":"Genaro R.","family":"Villa","sequence":"additional","affiliation":[{"name":"Harvey Cushing Neuro-Oncology Laboratories, Department of Neurosurgery, Brigham and Women\u2019s Hospital, Boston, MA 02115, USA"},{"name":"Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7608-4579","authenticated-orcid":false,"given":"Marco","family":"Mineo","sequence":"additional","affiliation":[{"name":"Harvey Cushing Neuro-Oncology Laboratories, Department of Neurosurgery, Brigham and Women\u2019s Hospital, Boston, MA 02115, USA"},{"name":"Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.1093\/neuonc\/noab106","article-title":"The 2021 WHO Classification of Tumors of the Central Nervous System: A summary","volume":"23","author":"Louis","year":"2021","journal-title":"Neuro Oncol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.ccr.2009.12.020","article-title":"Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1","volume":"17","author":"Verhaak","year":"2010","journal-title":"Cancer Cell"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1056\/NEJMra0708126","article-title":"Malignant gliomas in adults","volume":"359","author":"Wen","year":"2008","journal-title":"N. Engl. J. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1158\/2159-8290.CD-21-1059","article-title":"Hallmarks of Cancer: New Dimensions","volume":"12","author":"Hanahan","year":"2022","journal-title":"Cancer Discov."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1016\/j.cell.2011.02.013","article-title":"Hallmarks of cancer: The next generation","volume":"144","author":"Hanahan","year":"2011","journal-title":"Cell"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Torrisi, F., Alberghina, C., D\u2019Aprile, S., Pavone, A.M., Longhitano, L., Giallongo, S., Tibullo, D., Di Rosa, M., Zappala, A., and Cammarata, F.P. (2022). The Hallmarks of Glioblastoma: Heterogeneity, Intercellular Crosstalk and Molecular Signature of Invasiveness and Progression. Biomedicines, 10.","DOI":"10.3390\/biomedicines10040806"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1038\/s41580-022-00566-8","article-title":"Long non-coding RNAs: Definitions, functions, challenges and recommendations","volume":"24","author":"Mattick","year":"2023","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/15476286.2025.2530797","article-title":"The hidden power of antisense long non-coding RNAs: A dive into a novel regulatory layer mediated by double-stranded RNA formation","volume":"22","author":"Lamping","year":"2025","journal-title":"RNA Biol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1775","DOI":"10.1101\/gr.132159.111","article-title":"The GENCODE v7 catalog of human long noncoding RNAs: Analysis of their gene structure, evolution, and expression","volume":"22","author":"Derrien","year":"2012","journal-title":"Genome Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"D308","DOI":"10.1093\/nar\/gkx1107","article-title":"NONCODEV5: A comprehensive annotation database for long non-coding RNAs","volume":"46","author":"Fang","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1038\/s41576-018-0017-y","article-title":"Towards a complete map of the human long non-coding RNA transcriptome","volume":"19","author":"Lagarde","year":"2018","journal-title":"Nat. Rev. Genet."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1046\/j.1525-142X.2002.01069.x","article-title":"The g-value paradox","volume":"4","author":"Hahn","year":"2002","journal-title":"Evol. Dev."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1526","DOI":"10.1242\/jeb.005017","article-title":"A new paradigm for developmental biology","volume":"210","author":"Mattick","year":"2007","journal-title":"J. Exp. Biol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"3965","DOI":"10.1158\/0008-5472.CAN-16-2634","article-title":"Long Noncoding RNA and Cancer: A New Paradigm","volume":"77","author":"Bhan","year":"2017","journal-title":"Cancer Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"908","DOI":"10.1038\/nsmb.2591","article-title":"Integrative genomic analyses reveal clinically relevant long noncoding RNAs in human cancer","volume":"20","author":"Du","year":"2013","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1038\/s41580-020-00315-9","article-title":"Gene regulation by long non-coding RNAs and its biological functions","volume":"22","author":"Statello","year":"2021","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1016\/j.ccell.2016.03.010","article-title":"Long Noncoding RNAs in Cancer Pathways","volume":"29","author":"Schmitt","year":"2016","journal-title":"Cancer Cell"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1186\/s12943-018-0812-2","article-title":"New insights into long noncoding RNAs and their roles in glioma","volume":"17","author":"Peng","year":"2018","journal-title":"Mol. Cancer"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Rezaei, O., Tamizkar, K.H., Sharifi, G., Taheri, M., and Ghafouri-Fard, S. (2020). Emerging Role of Long Non-Coding RNAs in the Pathobiology of Glioblastoma. Front. Oncol., 10.","DOI":"10.3389\/fonc.2020.625884"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1104","DOI":"10.1227\/neu.0000000000002449","article-title":"The Role of Long Noncoding Ribonucleic Acids in Glioblastoma: What the Neurosurgeon Should Know","volume":"92","author":"Villa","year":"2023","journal-title":"Neurosurgery"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2500","DOI":"10.1016\/j.celrep.2016.05.018","article-title":"The Long Non-coding RNA HIF1A-AS2 Facilitates the Maintenance of Mesenchymal Glioblastoma Stem-like Cells in Hypoxic Niches","volume":"15","author":"Mineo","year":"2016","journal-title":"Cell Rep."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1002\/1878-0261.12413","article-title":"Long noncoding RNAs as regulators of cancer immunity","volume":"13","author":"Denaro","year":"2019","journal-title":"Mol. Oncol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1016\/j.molcel.2022.01.001","article-title":"SPARCLE, a p53-induced lncRNA, controls apoptosis after genotoxic stress by promoting PARP-1 cleavage","volume":"82","author":"Miao","year":"2022","journal-title":"Mol. Cell"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2925","DOI":"10.1042\/BCJ20170280","article-title":"The role of interactions of long non-coding RNAs and heterogeneous nuclear ribonucleoproteins in regulating cellular functions","volume":"474","author":"Sun","year":"2017","journal-title":"Biochem. J."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1002\/cac2.12254","article-title":"New insights into the interplay between long non-coding RNAs and RNA-binding proteins in cancer","volume":"42","author":"Yao","year":"2022","journal-title":"Cancer Commun."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1038\/s41576-020-00302-y","article-title":"RNA-binding proteins in human genetic disease","volume":"22","author":"Gebauer","year":"2021","journal-title":"Nat. Rev. Genet."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"6868","DOI":"10.1158\/1078-0432.CCR-19-0747","article-title":"Long Noncoding RNA SChLAP1 Forms a Growth-Promoting Complex with HNRNPL in Human Glioblastoma through Stabilization of ACTN4 and Activation of NF-kappaB Signaling","volume":"25","author":"Ji","year":"2019","journal-title":"Clin. Cancer Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1038\/s41418-022-01045-5","article-title":"N(6)-Methyladenosine-modified lncRNA LINREP promotes Glioblastoma progression by recruiting the PTBP1\/HuR complex","volume":"30","author":"Ji","year":"2023","journal-title":"Cell Death Differ."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1032","DOI":"10.1038\/s41419-020-03247-6","article-title":"LncRNA LINC00998 inhibits the malignant glioma phenotype via the CBX3-mediated c-Met\/Akt\/mTOR axis","volume":"11","author":"Cai","year":"2020","journal-title":"Cell Death Dis."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.biocel.2019.06.003","article-title":"The RNA-binding protein SRSF1 is a key cell cycle regulator via stabilizing NEAT1 in glioma","volume":"113","author":"Zhou","year":"2019","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1016\/j.omtn.2019.10.043","article-title":"LINC00680 and TTN-AS1 Stabilized by EIF4A3 Promoted Malignant Biological Behaviors of Glioblastoma Cells","volume":"19","author":"Tang","year":"2020","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1038\/s41419-019-1845-1","article-title":"UPF1 regulates the malignant biological behaviors of glioblastoma cells via enhancing the stability of Linc-00313","volume":"10","author":"Shao","year":"2019","journal-title":"Cell Death Dis."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1186\/s12967-023-04624-3","article-title":"METTL3-mediated HOTAIRM1 promotes vasculogenic mimicry icontributionsn glioma via regulating IGFBP2 expression","volume":"21","author":"Wu","year":"2023","journal-title":"J. Transl. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2912","DOI":"10.7150\/ijbs.58035","article-title":"SUMOylation of IGF2BP2 promotes vasculogenic mimicry of glioma via regulating OIP5-AS1\/miR-495-3p axis","volume":"17","author":"Li","year":"2021","journal-title":"Int. J. Biol. Sci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1007\/s10565-021-09614-z","article-title":"Long non-coding RNA OIP5-AS1 inhibition upregulates microRNA-129-5p to repress resistance to temozolomide in glioblastoma cells via downregulating IGF2BP2","volume":"38","author":"Wang","year":"2022","journal-title":"Cell Biol. Toxicol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1186\/s13046-019-1073-7","article-title":"ZRANB2\/SNHG20\/FOXK1 Axis regulates Vasculogenic mimicry formation in glioma","volume":"38","author":"Li","year":"2019","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1016\/j.omto.2020.03.017","article-title":"The PABPC5\/HCG15\/ZNF331 Feedback Loop Regulates Vasculogenic Mimicry of Glioma via STAU1-Mediated mRNA Decay","volume":"17","author":"Jing","year":"2020","journal-title":"Mol. Ther. Oncolytics"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1111\/jcmm.17106","article-title":"LOXL1-AS1 communicating with TIAR modulates vasculogenic mimicry in glioma via regulation of the miR-374b-5p\/MMP14 axis","volume":"26","author":"Yi","year":"2022","journal-title":"J. Cell. Mol. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1038\/s41419-021-03432-1","article-title":"HNRNPD interacts with ZHX2 regulating the vasculogenic mimicry formation of glioma cells via linc00707\/miR-651-3p\/SP2 axis","volume":"12","author":"Yu","year":"2021","journal-title":"Cell Death Dis."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1388","DOI":"10.1093\/neuonc\/noae036","article-title":"Long non-coding RNA lung cancer-associated transcript-1 promotes glioblastoma progression by enhancing Hypoxia-inducible factor 1 alpha activity","volume":"26","author":"Huang","year":"2024","journal-title":"Neuro Oncol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1038\/s41419-020-2650-6","article-title":"Lin28A promotes IRF6-regulated aerobic glycolysis in glioma cells by stabilizing SNHG14","volume":"11","author":"Lu","year":"2020","journal-title":"Cell Death Dis."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1038\/s41420-021-00674-y","article-title":"m(6)A reader IGF2BP2-stabilized CASC9 accelerates glioblastoma aerobic glycolysis by enhancing HK2 mRNA stability","volume":"7","author":"Liu","year":"2021","journal-title":"Cell Death Discov."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1186\/s13045-018-0619-z","article-title":"A cytoplasmic long noncoding RNA LINC00470 as a new AKT activator to mediate glioblastoma cell autophagy","volume":"11","author":"Liu","year":"2018","journal-title":"J. Hematol. Oncol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.canlet.2020.10.047","article-title":"lncRNA LINC01057 promotes mesenchymal differentiation by activating NF-kappaB signaling in glioblastoma","volume":"498","author":"Tang","year":"2021","journal-title":"Cancer Lett."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"3310","DOI":"10.7150\/thno.82590","article-title":"SPI1-mediated MIR222HG transcription promotes proneural-to-mesenchymal transition of glioma stem cells and immunosuppressive polarization of macrophages","volume":"13","author":"Fan","year":"2023","journal-title":"Theranostics"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1271","DOI":"10.1007\/s10571-020-00898-z","article-title":"LncRNA MIR155HG Promotes Temozolomide Resistance by Activating the Wnt\/beta-Catenin Pathway Via Binding to PTBP1 in Glioma","volume":"41","author":"He","year":"2021","journal-title":"Cell. Mol. Neurobiol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"952","DOI":"10.1038\/s41419-021-04245-y","article-title":"A positive feedback loop of lncRNA-RMRP\/ZNRF3 axis and Wnt\/beta-catenin signaling regulates the progression and temozolomide resistance in glioma","volume":"12","author":"Liu","year":"2021","journal-title":"Cell Death Dis."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Han, J., Yu, X., Wang, S., Wang, Y., Liu, Q., Xu, H., and Wang, X. (2021). IGF2BP2 Induces U251 Glioblastoma Cell Chemoresistance by Inhibiting FOXO1-Mediated PID1 Expression Through Stabilizing lncRNA DANCR. Front. Cell Dev. Biol., 9.","DOI":"10.3389\/fcell.2021.659228"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.brainresbull.2022.04.005","article-title":"Long non-coding RNA ATXN8OS promotes ferroptosis and inhibits the temozolomide-resistance of gliomas through the ADAR\/GLS2 pathway","volume":"186","author":"Luo","year":"2022","journal-title":"Brain Res. Bull."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1186\/s12935-022-02659-y","article-title":"STAT3-mediated upregulation of LINC00520 contributed to temozolomide chemoresistance in glioblastoma by interacting with RNA-binding protein LIN28B","volume":"22","author":"Yuan","year":"2022","journal-title":"Cancer Cell Int."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"eadf3984","DOI":"10.1126\/sciadv.adf3984","article-title":"Multiomics analyses reveal DARS1-AS1\/YBX1-controlled posttranscriptional circuits promoting glioblastoma tumorigenesis\/radioresistance","volume":"9","author":"Zheng","year":"2023","journal-title":"Sci. Adv."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1038\/s41419-023-05933-7","article-title":"METTL3-mediated m6A modification of LINC00839 maintains glioma stem cells and radiation resistance by activating Wnt\/beta-catenin signaling","volume":"14","author":"Yin","year":"2023","journal-title":"Cell Death Dis."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1777","DOI":"10.1080\/15476286.2020.1795583","article-title":"IGF2BP2 stabilized FBXL19-AS1 regulates the blood-tumour barrier permeability by negatively regulating ZNF765 by STAU1-mediated mRNA decay","volume":"17","author":"Liu","year":"2020","journal-title":"RNA Biol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"9941","DOI":"10.1096\/fj.202000045R","article-title":"Lnc00462717 regulates the permeability of the blood-brain tumor barrier through interaction with PTBP1 to inhibit the miR-186-5p\/Occludin signaling pathway","volume":"34","author":"Zhang","year":"2020","journal-title":"FASEB J."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1207","DOI":"10.1016\/j.molcel.2020.05.015","article-title":"Tumor Interferon Signaling Is Regulated by a lncRNA INCR1 Transcribed from the PD-L1 Locus","volume":"78","author":"Mineo","year":"2020","journal-title":"Mol. Cell"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Yi, K., Cui, X., Liu, X., Wang, Y., Zhao, J., Yang, S., Xu, C., Yang, E., Xiao, M., and Hong, B. (2021). PTRF\/Cavin-1 as a Novel RNA-Binding Protein Expedites the NF-kappaB\/PD-L1 Axis by Stabilizing lncRNA NEAT1, Contributing to Tumorigenesis and Immune Evasion in Glioblastoma. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.802795"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/S0092-8674(00)81683-9","article-title":"The hallmarks of cancer","volume":"100","author":"Hanahan","year":"2000","journal-title":"Cell"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1001\/jama.2023.0023","article-title":"Glioblastoma and Other Primary Brain Malignancies in Adults: A Review","volume":"329","author":"Schaff","year":"2023","journal-title":"JAMA"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1564","DOI":"10.1016\/S0140-6736(23)01054-1","article-title":"Primary brain tumours in adults","volume":"402","author":"Geurts","year":"2023","journal-title":"Lancet"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1038\/s41580-021-00404-3","article-title":"Cell cycle control in cancer","volume":"23","author":"Matthews","year":"2022","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"3843","DOI":"10.1128\/MCB.00758-14","article-title":"Plakophilin-2 promotes tumor development by enhancing ligand-dependent and -independent epidermal growth factor receptor dimerization and activation","volume":"34","author":"Arimoto","year":"2014","journal-title":"Mol. Cell. Biol."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Park, J.H., and Lee, H.K. (2022). Current Understanding of Hypoxia in Glioblastoma Multiforme and Its Response to Immunotherapy. Cancers, 14.","DOI":"10.3390\/cancers14051176"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1093\/neuonc\/now258","article-title":"Hypoxia in the glioblastoma microenvironment: Shaping the phenotype of cancer stem-like cells","volume":"19","author":"Colwell","year":"2017","journal-title":"Neuro Oncol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1111\/cas.15240","article-title":"Hypoxia-inducible lncRNA MIR210HG interacting with OCT1 is involved in glioblastoma multiforme malignancy","volume":"113","author":"Ho","year":"2022","journal-title":"Cancer Sci."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1038\/s41392-023-01481-w","article-title":"The blood-brain barrier: Structure, regulation, and drug delivery","volume":"8","author":"Wu","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1038\/s41568-019-0205-x","article-title":"The blood-brain barrier and blood-tumour barrier in brain tumours and metastases","volume":"20","author":"Arvanitis","year":"2020","journal-title":"Nat. Rev. Cancer"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Ballato, M., Germana, E., Ricciardi, G., Giordano, W.G., Tralongo, P., Buccarelli, M., Castellani, G., Ricci-Vitiani, L., D\u2019Alessandris, Q.G., and Giuffre, G. (2025). Understanding Neovascularization in Glioblastoma: Insights from the Current Literature. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26062763"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1056\/NEJMoa1308345","article-title":"Bevacizumab plus radiotherapy-temozolomide for newly diagnosed glioblastoma","volume":"370","author":"Chinot","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1056\/NEJMoa1308573","article-title":"A randomized trial of bevacizumab for newly diagnosed glioblastoma","volume":"370","author":"Gilbert","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1007\/s11060-024-04865-2","article-title":"Angiogenesis inhibitors effects on overall survival and progression-free survival in newly diagnosed primary glioblastoma multiforme: A meta-analysis of twelve randomized clinical trials","volume":"171","author":"Mortezaei","year":"2025","journal-title":"J. Neurooncol."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"So, J.S., Kim, H., and Han, K.S. (2021). Mechanisms of Invasion in Glioblastoma: Extracellular Matrix, Ca(2+) Signaling, and Glutamate. Front. Cell. Neurosci., 15.","DOI":"10.3389\/fncel.2021.663092"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"6662","DOI":"10.1038\/s41467-025-61999-1","article-title":"The invasion phenotypes of glioblastoma depend on plastic and reprogrammable cell states","volume":"16","author":"Doroszko","year":"2025","journal-title":"Nat. Commun."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"864","DOI":"10.1007\/s10143-024-02944-6","article-title":"Glioblastoma invasion patterns from a clinical perspective-a systematic review","volume":"47","author":"Percuoco","year":"2024","journal-title":"Neurosurg. Rev."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"992","DOI":"10.1016\/j.cell.2011.11.016","article-title":"Cancer invasion and the microenvironment: Plasticity and reciprocity","volume":"147","author":"Friedl","year":"2011","journal-title":"Cell"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1007\/978-3-030-30651-9_7","article-title":"Signaling Determinants of Glioma Cell Invasion","volume":"1202","author":"Kwiatkowska","year":"2020","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1158\/1535-7163.MCT-22-0595","article-title":"Interplay Between Extracellular Matrix Remodeling and Angiogenesis in Tumor Ecosystem","volume":"22","author":"Siddhartha","year":"2023","journal-title":"Mol. Cancer Ther."},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Cortes Ballen, A.I., Amosu, M., Ravinder, S., Chan, J., Derin, E., Slika, H., and Tyler, B. (2024). Metabolic Reprogramming in Glioblastoma Multiforme: A Review of Pathways and Therapeutic Targets. Cells, 13.","DOI":"10.3390\/cells13181574"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1126\/science.1160809","article-title":"Understanding the Warburg effect: The metabolic requirements of cell proliferation","volume":"324","author":"Cantley","year":"2009","journal-title":"Science"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"5478","DOI":"10.1158\/0008-5472.CAN-19-3923","article-title":"Brain Tumor Stem Cell Dependence on Glutaminase Reveals a Metabolic Vulnerability through the Amino Acid Deprivation Response Pathway","volume":"80","author":"Restall","year":"2020","journal-title":"Cancer Res."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"289","DOI":"10.2217\/cns.13.20","article-title":"Lipid metabolism emerges as a promising target for malignant glioma therapy","volume":"2","author":"Guo","year":"2013","journal-title":"CNS Oncol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"101569","DOI":"10.1016\/j.isci.2020.101569","article-title":"Lipid Droplets Maintain Energy Homeostasis and Glioblastoma Growth via Autophagic Release of Stored Fatty Acids","volume":"23","author":"Wu","year":"2020","journal-title":"iScience"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"19593","DOI":"10.1038\/s41598-019-55985-z","article-title":"Lipid accumulation and oxidation in glioblastoma multiforme","volume":"9","author":"Taib","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1759091418818261","DOI":"10.1177\/1759091418818261","article-title":"Mitochondrial Substrate-Level Phosphorylation as Energy Source for Glioblastoma: Review and Hypothesis","volume":"10","author":"Chinopoulos","year":"2018","journal-title":"ASN Neuro"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"153","DOI":"10.3892\/or.2022.8365","article-title":"Research progress on the interaction between long non-coding RNAs and RNA-binding proteins to influence the reprogramming of tumor glucose metabolism (Review)","volume":"48","author":"Wu","year":"2022","journal-title":"Oncol. Rep."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1007\/s13238-020-00725-7","article-title":"Regulation of aerobic glycolysis to decelerate tumor proliferation by small molecule inhibitors targeting glucose transporters","volume":"11","author":"Gao","year":"2020","journal-title":"Protein Cell"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1038\/nature08697","article-title":"HnRNP proteins controlled by c-Myc deregulate pyruvate kinase mRNA splicing in cancer","volume":"463","author":"David","year":"2010","journal-title":"Nature"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1016\/S0167-4889(97)00150-X","article-title":"Evolution and regulatory role of the hexokinases","volume":"1401","author":"Cardenas","year":"1998","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"2049","DOI":"10.1242\/jeb.00241","article-title":"Isozymes of mammalian hexokinase: Structure, subcellular localization and metabolic function","volume":"206","author":"Wilson","year":"2003","journal-title":"J. Exp. Biol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.semcancer.2024.03.001","article-title":"GLUT and HK: Two primary and essential key players in tumor glycolysis","volume":"100","author":"Yadav","year":"2024","journal-title":"Semin. Cancer Biol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"189557","DOI":"10.1016\/j.bbcan.2026.189557","article-title":"Glioblastoma cell plasticity: A new paradigm in glioblastoma therapeutic resistance","volume":"1881","author":"Xiao","year":"2026","journal-title":"Biochim. Biophys. Acta Rev. Cancer"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1038\/s41525-019-0108-5","article-title":"Proneural and mesenchymal glioma stem cells display major differences in splicing and lncRNA profiles","volume":"5","author":"Guardia","year":"2020","journal-title":"NPJ Genom. Med."},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Reon, B.J., Anaya, J., Zhang, Y., Mandell, J., Purow, B., Abounader, R., and Dutta, A. (2016). Expression of lncRNAs in Low-Grade Gliomas and Glioblastoma Multiforme: An In Silico Analysis. PLoS Med., 13.","DOI":"10.1371\/journal.pmed.1002192"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1016\/j.cell.2019.06.024","article-title":"An Integrative Model of Cellular States, Plasticity, and Genetics for Glioblastoma","volume":"178","author":"Neftel","year":"2019","journal-title":"Cell"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"2485","DOI":"10.1016\/j.cell.2024.03.029","article-title":"Integrative spatial analysis reveals a multi-layered organization of glioblastoma","volume":"187","author":"Greenwald","year":"2024","journal-title":"Cell"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"19731","DOI":"10.1038\/s41598-025-04862-z","article-title":"Machine learning and multi-omics analysis reveal key regulators of proneural-mesenchymal transition in glioblastoma","volume":"15","author":"Xu","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1186\/s12967-020-02552-0","article-title":"Profiling pro-neural to mesenchymal transition identifies a lncRNA signature in glioma","volume":"18","author":"Liang","year":"2020","journal-title":"J. Transl. Med."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1056\/NEJMoa043330","article-title":"Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma","volume":"352","author":"Stupp","year":"2005","journal-title":"N. Engl. J. Med."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"107922","DOI":"10.1016\/j.pharmthera.2021.107922","article-title":"Genotoxic therapy and resistance mechanism in gliomas","volume":"228","author":"Lang","year":"2021","journal-title":"Pharmacol. Ther."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1781","DOI":"10.1038\/s41388-025-03454-5","article-title":"Post-translational modifications in DNA damage repair: Mechanisms underlying temozolomide resistance in glioblastoma","volume":"44","author":"Chen","year":"2025","journal-title":"Oncogene"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1186\/s40478-025-02046-4","article-title":"Overcoming temozolomide resistance in glioma: Recent advances and mechanistic insights","volume":"13","author":"Li","year":"2025","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Eckerdt, F., and Platanias, L.C. (2023). Emerging Role of Glioma Stem Cells in Mechanisms of Therapy Resistance. Cancers, 15.","DOI":"10.3390\/cancers15133458"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"2217","DOI":"10.1002\/jcp.27186","article-title":"Wnt\/beta-catenin signaling cascade: A promising target for glioma therapy","volume":"234","author":"He","year":"2019","journal-title":"J. Cell. Physiol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1124\/mol.119.117978","article-title":"Wnt Signaling and Drug Resistance in Cancer","volume":"97","author":"Zhong","year":"2020","journal-title":"Mol. Pharmacol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1038\/s41598-017-00947-6","article-title":"PID1 increases chemotherapy-induced apoptosis in medulloblastoma and glioblastoma cells in a manner that involves NFkappaB","volume":"7","author":"Xu","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1038\/nature12477","article-title":"Signatures of mutational processes in human cancer","volume":"500","author":"Alexandrov","year":"2013","journal-title":"Nature"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"101385","DOI":"10.1016\/j.smim.2020.101385","article-title":"Tumor antigens in glioma","volume":"47","author":"Nejo","year":"2020","journal-title":"Semin. Immunol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"4175","DOI":"10.1158\/1078-0432.CCR-17-1846","article-title":"T-Cell Exhaustion Signatures Vary with Tumor Type and Are Severe in Glioblastoma","volume":"24","author":"Woroniecka","year":"2018","journal-title":"Clin. Cancer Res."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"1459","DOI":"10.1038\/s41591-018-0135-2","article-title":"Sequestration of T cells in bone marrow in the setting of glioblastoma and other intracranial tumors","volume":"24","author":"Chongsathidkiet","year":"2018","journal-title":"Nat. Med."},{"key":"ref_109","doi-asserted-by":"crossref","unstructured":"Himes, B.T., Geiger, P.A., Ayasoufi, K., Bhargav, A.G., Brown, D.A., and Parney, I.F. (2021). Immunosuppression in Glioblastoma: Current Understanding and Therapeutic Implications. Front. Oncol., 11.","DOI":"10.3389\/fonc.2021.770561"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"1272","DOI":"10.1016\/j.apsb.2026.01.015","article-title":"Targeting immunosuppressive network in glioblastoma: Emerging strategies to overcome immunodeficiency and enhance therapeutic efficacy","volume":"16","author":"Zhou","year":"2026","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1215\/15228517-2006-006","article-title":"An increase in CD4+CD25+FOXP3+ regulatory T cells in tumor-infiltrating lymphocytes of human glioblastoma multiforme","volume":"8","author":"Lesniak","year":"2006","journal-title":"Neuro Oncol."},{"key":"ref_112","doi-asserted-by":"crossref","unstructured":"Magri, S., Musca, B., Bonaudo, C., Tushe, A., Russo, M.G., Masetto, E., Zagonel, V., Lombardi, G., Della Puppa, A., and Mandruzzato, S. (2021). Sustained Accumulation of Blood-Derived Macrophages in the Immune Microenvironment of Patients with Recurrent Glioblastoma after Therapy. Cancers, 13.","DOI":"10.3390\/cancers13246178"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"3167","DOI":"10.1002\/1878-0261.13287","article-title":"Elucidating tumour-associated microglia\/macrophage diversity along glioblastoma progression and under ACOD1 deficiency","volume":"16","author":"Muller","year":"2022","journal-title":"Mol. Oncol."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"1100","DOI":"10.1038\/s41590-019-0433-y","article-title":"Mechanisms of immunotherapy resistance: Lessons from glioblastoma","volume":"20","author":"Jackson","year":"2019","journal-title":"Nat. Immunol."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1001\/jamaoncol.2020.1024","article-title":"Effect of Nivolumab vs. Bevacizumab in Patients With Recurrent Glioblastoma: The CheckMate 143 Phase 3 Randomized Clinical Trial","volume":"6","author":"Reardon","year":"2020","journal-title":"JAMA Oncol."},{"key":"ref_116","first-page":"201","article-title":"Immunotherapy for glioblastoma: On the sidelines or in the game?","volume":"24","author":"Reardon","year":"2017","journal-title":"Discov. Med."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1093\/neuonc\/nox208","article-title":"Nivolumab with or without ipilimumab in patients with recurrent glioblastoma: Results from exploratory phase I cohorts of CheckMate 143","volume":"20","author":"Omuro","year":"2018","journal-title":"Neuro Oncol."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1093\/neuonc\/noaa277","article-title":"Unique challenges for glioblastoma immunotherapy-discussions across neuro-oncology and non-neuro-oncology experts in cancer immunology. Meeting Report from the 2019 SNO Immuno-Oncology Think Tank","volume":"23","author":"Chuntova","year":"2021","journal-title":"Neuro Oncol."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"111208","DOI":"10.1016\/j.jbc.2026.111208","article-title":"The RNA-binding protein MSI2 controls blood-tumor barrier permeability via LINC00667-Mediated IRF6 mRNA decay","volume":"302","author":"Gao","year":"2026","journal-title":"J. Biol. Chem."},{"key":"ref_120","doi-asserted-by":"crossref","unstructured":"Zhang, M., Hutter, G., Kahn, S.A., Azad, T.D., Gholamin, S., Xu, C.Y., Liu, J., Achrol, A.S., Richard, C., and Sommerkamp, P. (2016). Anti-CD47 Treatment Stimulates Phagocytosis of Glioblastoma by M1 and M2 Polarized Macrophages and Promotes M1 Polarized Macrophages In Vivo. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0153550"},{"key":"ref_121","doi-asserted-by":"crossref","unstructured":"Hao, C., Chen, G., Zhao, H., Li, Y., Chen, J., Zhang, H., Li, S., Zhao, Y., Chen, F., and Li, W. (2020). PD-L1 Expression in Glioblastoma, the Clinical and Prognostic Significance: A Systematic Literature Review and Meta-Analysis. Front. Oncol., 10.","DOI":"10.3389\/fonc.2020.01015"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1016\/j.immuni.2018.03.014","article-title":"Regulation and Function of the PD-L1 Checkpoint","volume":"48","author":"Sun","year":"2018","journal-title":"Immunity"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1093\/annonc\/mdz006","article-title":"The Macrophage \u2018Do not eat me\u2019 signal, CD47, is a clinically validated cancer immunotherapy target","volume":"30","author":"Takimoto","year":"2019","journal-title":"Ann. Oncol."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1007\/s11060-025-04978-2","article-title":"Improving IL12 immunotherapy in glioblastoma by targeting the long noncoding RNA INCR1","volume":"173","author":"Saini","year":"2025","journal-title":"J. Neurooncol."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"14802","DOI":"10.1038\/ncomms14802","article-title":"A CD47-associated super-enhancer links pro-inflammatory signalling to CD47 upregulation in breast cancer","volume":"8","author":"Betancur","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_126","doi-asserted-by":"crossref","unstructured":"Pan, T., Xie, D.K., Li, J., Qiang, Y.J., Fan, S.Y., Wang, T.T., Han, Y.Y., Zang, J., Yang, Y., and Zhao, J.L. (2024). Glioma-Stem-Cell-Derived Exosomes Remodeled Glioma-Associated Macrophage via NEAT1\/miR-125a\/STAT3 Pathway. Cancers, 16.","DOI":"10.3390\/cancers16142500"},{"key":"ref_127","doi-asserted-by":"crossref","unstructured":"Wang, G., Zhong, K., Wang, Z., Zhang, Z., Tang, X., Tong, A., and Zhou, L. (2022). Tumor-associated microglia and macrophages in glioblastoma: From basic insights to therapeutic opportunities. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.964898"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"2226","DOI":"10.1158\/1078-0432.CCR-22-3714","article-title":"Clinical Importance of the lncRNA NEAT1 in Cancer Patients Treated with Immune Checkpoint Inhibitors","volume":"29","author":"Toker","year":"2023","journal-title":"Clin. Cancer Res."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"C252","DOI":"10.1152\/ajpcell.00234.2023","article-title":"Cancer-associated fibroblast-associated gene IGFBP2 promotes glioma progression through induction of M2 macrophage polarization","volume":"326","author":"Zhang","year":"2024","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_130","doi-asserted-by":"crossref","unstructured":"Liu, Y., Song, C., Shen, F., Zhang, J., and Song, S.W. (2019). IGFBP2 promotes immunosuppression associated with its mesenchymal induction and FcgammaRIIB phosphorylation in glioblastoma. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0222999"},{"key":"ref_131","doi-asserted-by":"crossref","unstructured":"Dhuri, K., Bechtold, C., Quijano, E., Pham, H., Gupta, A., Vikram, A., and Bahal, R. (2020). Antisense Oligonucleotides: An Emerging Area in Drug Discovery and Development. J. Clin. Med., 9.","DOI":"10.3390\/jcm9062004"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1146\/annurev-pharmtox-010716-104846","article-title":"Pharmacology of Antisense Drugs","volume":"57","author":"Bennett","year":"2017","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1038\/nbt.3802","article-title":"Overcoming cellular barriers for RNA therapeutics","volume":"35","author":"Dowdy","year":"2017","journal-title":"Nat. Biotechnol."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1089\/nat.2014.0506","article-title":"Phosphorothioates, essential components of therapeutic oligonucleotides","volume":"24","author":"Eckstein","year":"2014","journal-title":"Nucleic Acid. Ther."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1146\/annurev.pa.36.040196.000543","article-title":"Progress in antisense oligonucleotide therapeutics","volume":"36","author":"Crooke","year":"1996","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"6518","DOI":"10.1093\/nar\/gkw236","article-title":"The delivery of therapeutic oligonucleotides","volume":"44","author":"Juliano","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/S0169-328X(97)00048-X","article-title":"End-capped antisense oligodeoxynucleotides effectively inhibit gene expression in vivo and offer a low-toxicity alternative to fully modified phosphorothioate oligodeoxynucleotides","volume":"47","author":"Hebb","year":"1997","journal-title":"Brain Res. Mol. Brain Res."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S1074-5521(00)00058-2","article-title":"Locked nucleic acid (LNA): Fine-tuning the recognition of DNA and RNA","volume":"8","author":"Braasch","year":"2001","journal-title":"Chem. Biol."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/S0167-4781(99)00148-7","article-title":"Molecular mechanisms of action of antisense drugs","volume":"1489","author":"Crooke","year":"1999","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1146\/annurev.pharmtox.010909.105654","article-title":"RNA targeting therapeutics: Molecular mechanisms of antisense oligonucleotides as a therapeutic platform","volume":"50","author":"Bennett","year":"2010","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1124\/jpet.113.212407","article-title":"Pharmacology of a central nervous system delivered 2\u2032-O-methoxyethyl-modified survival of motor neuron splicing oligonucleotide in mice and nonhuman primates","volume":"350","author":"Rigo","year":"2014","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1056\/NEJMoa1710504","article-title":"Nusinersen versus Sham Control in Later-Onset Spinal Muscular Atrophy","volume":"378","author":"Mercuri","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1038\/s41573-022-00521-4","article-title":"Targeting RNA structures with small molecules","volume":"21","author":"Yang","year":"2022","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_144","doi-asserted-by":"crossref","unstructured":"Konde, O.M., Balela, W.B., and Tshitenge, T.B. (2025). Targeting RNA-binding proteins with small molecules: Perspectives and challenges. Front. Chem., 13.","DOI":"10.3389\/fchem.2025.1649692"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1016\/j.tips.2025.06.007","article-title":"Structure-function-guided drug development efforts to target lncRNAs","volume":"46","author":"Watmuff","year":"2025","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_146","doi-asserted-by":"crossref","unstructured":"Carabet, L.A., Leblanc, E., Lallous, N., Morin, H., Ghaidi, F., Lee, J., Rennie, P.S., and Cherkasov, A. (2019). Computer-Aided Discovery of Small Molecules Targeting the RNA Splicing Activity of hnRNP A1 in Castration-Resistant Prostate Cancer. Molecules, 24.","DOI":"10.3390\/molecules24040763"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"656","DOI":"10.33594\/000000164","article-title":"A Novel Probe for Spliceosomal Proteins that Induces Autophagy and Death of Melanoma Cells Reveals New Targets for Melanoma Drug Discovery","volume":"53","author":"Palrasu","year":"2019","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_148","doi-asserted-by":"crossref","unstructured":"Velayutham, S., Seal, T., Danthurthy, S., Zaias, J., Smalley, K.S.M., and Minond, D. (2023). In Vivo Acute Toxicity Studies of Novel Anti-Melanoma Compounds Downregulators of hnRNPH1\/H2. Biomolecules, 13.","DOI":"10.3390\/biom13020349"},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"134946","DOI":"10.1016\/j.ijbiomac.2024.134946","article-title":"G-quadruplexes in long non-coding RNAs and their interactions with proteins","volume":"278","author":"Shukla","year":"2024","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1093\/nar\/gkab1208","article-title":"Identification and targeting of G-quadruplex structures in MALAT1 long non-coding RNA","volume":"50","author":"Mou","year":"2022","journal-title":"Nucleic Acids Res."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"1047","DOI":"10.1016\/j.chembiol.2019.07.015","article-title":"RIBOTACs: Small Molecules Target RNA for Degradation","volume":"26","author":"Dey","year":"2019","journal-title":"Cell Chem. Biol."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"e12715","DOI":"10.1002\/advs.202512715","article-title":"RNA G-Quadruplex RIBOTAC-Mediated Targeted Degradation of lncRNA TERRA","volume":"12","author":"Khaskia","year":"2025","journal-title":"Adv. Sci."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1038\/s41573-021-00371-6","article-title":"PROTAC targeted protein degraders: The past is prologue","volume":"21","author":"Bekes","year":"2022","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"3163","DOI":"10.1002\/anie.202012330","article-title":"RNA-PROTACs: Degraders of RNA-Binding Proteins","volume":"60","author":"Ghidini","year":"2021","journal-title":"Angew. Chem. Int. Ed. Engl."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"117299","DOI":"10.1016\/j.bmc.2023.117299","article-title":"The aptamer-based RNA-PROTAC","volume":"86","author":"Xu","year":"2023","journal-title":"Bioorg. Med. Chem."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"4567","DOI":"10.1021\/acs.jmedchem.5c03203","article-title":"Targeted Degradation of Lin28B Using Pre-let-7-PROTACs for Hepatocellular Carcinoma Therapy","volume":"69","author":"Xu","year":"2026","journal-title":"J. Med. Chem."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"e2400427","DOI":"10.1002\/mabi.202400427","article-title":"PROTAC and Molecular Glue Degraders of the Oncogenic RNA Binding Protein Lin28","volume":"25","author":"Kashkush","year":"2025","journal-title":"Macromol. Biosci."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1007\/s10571-025-01608-3","article-title":"Integrated Bioinformatics Analysis of Differentially Expressed RNA-Binding Proteins in Human Gliomas","volume":"46","author":"Haque","year":"2025","journal-title":"Cell. Mol. Neurobiol."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"115876","DOI":"10.1016\/j.addr.2026.115876","article-title":"Engineering brain-penetrant PROTACs: Bridging molecular design and CNS delivery","volume":"234","author":"Li","year":"2026","journal-title":"Adv. Drug Deliv. 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