{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T11:29:42Z","timestamp":1786706982410,"version":"build-2736575974"},"reference-count":78,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T00:00:00Z","timestamp":1786665600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Major Project of Guangzhou National Laboratory","award":["GZNL2023A02008"],"award-info":[{"award-number":["GZNL2023A02008"]}]},{"name":"Major Project of Guangzhou National Laboratory","award":["GZNL2024A03012"],"award-info":[{"award-number":["GZNL2024A03012"]}]},{"award":["GZNL2023A02008"],"award-info":[{"award-number":["GZNL2023A02008"]}],"id":[{"id":"https:\/\/ror.org\/03ybmxt82","id-type":"ROR","asserted-by":"publisher"}]},{"award":["GZNL2024A03012"],"award-info":[{"award-number":["GZNL2024A03012"]}],"id":[{"id":"https:\/\/ror.org\/03ybmxt82","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Guangzhou National Laboratory and State Key Laboratory of Respiratory Disease","award":["GZNL2025B01010"],"award-info":[{"award-number":["GZNL2025B01010"]}]},{"award":["GZNL2025B01010"],"award-info":[{"award-number":["GZNL2025B01010"]}],"id":[{"id":"https:\/\/ror.org\/04hja5e04","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Guangzhou Federation of Trade Unions to the Frontiers and Advanced Technologies Innovation Studio for Stem Cell Regenerative Medicine","award":["GSGH01"],"award-info":[{"award-number":["GSGH01"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Lung cancer is characterized by profound molecular and clinical heterogeneity and remains the leading cause of cancer-related mortality worldwide. Its initiation and progression are shaped by complex genetic and epigenetic alterations that perturb key biological processes, including cell proliferation, apoptosis, metabolic reprogramming, invasion, metastasis, and immune evasion. Increasing evidence indicates that dysregulated alternative splicing (AS) represents a critical post-transcriptional regulatory mechanism involved in lung cancer pathogenesis. Although AS abnormalities are not the sole drivers of tumorigenesis, they contribute to malignant transformation, tumor progression, therapeutic resistance, and phenotypic plasticity, providing opportunities for biomarker development and therapeutic targeting. This review summarizes the multifaceted roles of AS in lung cancer biology, highlighting its contributions to tumor evolution, metastatic dissemination, and treatment resistance. Furthermore, subtype-specific AS landscapes between major lung cancer subtypes are discussed to elucidate their distinct molecular mechanisms and therapeutic implications. Representative AS-generated isoforms, including cluster of differentiation 44 variants (CD44v), are further discussed as examples of how aberrant splicing events regulate cancer stemness, tumor progression, and therapeutic responses. The regulatory mechanisms underlying CD44v generation, including upstream splicing factors and downstream signaling pathways, are also summarized. Collectively, this review highlights the emerging role of aberrant AS regulation in lung cancer and emphasizes its potential implications for biomarker discovery and precision therapeutic strategies targeting splicing dysregulation.<\/jats:p>","DOI":"10.3390\/ijms27167269","type":"journal-article","created":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T10:39:01Z","timestamp":1786703941000},"page":"7269","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Role of Alternative Splicing in Lung Cancer: Mechanisms, Regulators, and Therapeutic Implications"],"prefix":"10.3390","volume":"27","author":[{"given":"Lingrui","family":"Shang","sequence":"first","affiliation":[{"name":"School of Biomedical Engineering, Guangzhou Medical University, Guangzhou 511436, China"},{"name":"Department of Diagnostics and Detection Technologies, Guangzhou National Laboratory, Guangzhou 510005, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nannan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Diagnostics and Detection Technologies, Guangzhou National Laboratory, Guangzhou 510005, China"},{"name":"College of Life Science & Technology, Huazhong University of Science and Technology, Wuhan 430074, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qianqian","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Biomedical Engineering, Guangzhou Medical University, Guangzhou 511436, China"},{"name":"Department of Diagnostics and Detection Technologies, Guangzhou National Laboratory, Guangzhou 510005, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lihua","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Forestry and Biotechnology, Zhejiang A&F University, Hangzhou 311300, China"},{"name":"State Key Laboratory for Development and Utilization of Forest Food Resources, Zhejiang A&F University, Hangzhou 311300, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5371-7943","authenticated-orcid":false,"given":"Huisheng","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Biomedical Engineering, Guangzhou Medical University, Guangzhou 511436, China"},{"name":"Department of Diagnostics and Detection Technologies, Guangzhou National Laboratory, Guangzhou 510005, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1038\/s41571-025-01021-1","article-title":"Tumour and microenvironment crosstalk in NSCLC progression and response to therapy","volume":"22","author":"Rahal","year":"2025","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1186\/s13045-024-01631-9","article-title":"RAS signaling in carcinogenesis, cancer therapy and resistance mechanisms","volume":"17","author":"Yang","year":"2024","journal-title":"J. Hematol. Oncol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1803","DOI":"10.1016\/j.ccell.2024.09.006","article-title":"Lactylation in cancer: Current understanding and challenges","volume":"42","author":"Li","year":"2024","journal-title":"Cancer Cell"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.jhep.2023.10.006","article-title":"Endothelial DGKG promotes tumor angiogenesis and immune evasion in hepatocellular carcinoma","volume":"80","author":"Zhang","year":"2024","journal-title":"J. Hepatol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1186\/s13045-022-01292-6","article-title":"Hypoxia-inducible factors: Master regulators of hypoxic tumor immune escape","volume":"15","author":"Wu","year":"2022","journal-title":"J. Hematol. Oncol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e168123","DOI":"10.1172\/JCI166224","article-title":"CAP2 promotes gastric cancer metastasis by mediating the interaction between tumor cells and tumor-associated macrophages","volume":"133","author":"Zhang","year":"2023","journal-title":"J. Clin. Investig."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/S0140-6736(21)00312-3","article-title":"Lung cancer","volume":"398","author":"Thai","year":"2021","journal-title":"Lancet"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"937","DOI":"10.1002\/cac2.12359","article-title":"Non-small cell lung cancer in China","volume":"42","author":"Chen","year":"2022","journal-title":"Cancer Commun."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1159\/000487440","article-title":"Heterogeneity in lung cancer","volume":"85","author":"Carvalho","year":"2018","journal-title":"Pathobiology"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e006234","DOI":"10.1136\/jitc-2022-006234","article-title":"Spatial multi-omics revealed the impact of tumor ecosystem heterogeneity on immunotherapy efficacy in patients with advanced non-small cell lung cancer treated with bispecific antibody","volume":"11","author":"Song","year":"2023","journal-title":"J. Immunother. Cancer"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1186\/s13045-019-0818-2","article-title":"Emerging insights of tumor heterogeneity and drug resistance mechanisms in lung cancer targeted therapy","volume":"12","author":"Lim","year":"2019","journal-title":"J. Hematol. Oncol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"100728","DOI":"10.1016\/j.drup.2020.100728","article-title":"The role of alternative splicing in cancer: From oncogenesis to drug resistance","volume":"53","author":"Sciarrillo","year":"2020","journal-title":"Drug Resist. Updates"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"5382","DOI":"10.1038\/onc.2017.150","article-title":"Human DBR1 modulates the recycling of snRNPs to affect alternative RNA splicing and contributes to the suppression of cancer development","volume":"36","author":"Han","year":"2017","journal-title":"Oncogene"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1038\/s41388-020-01507-5","article-title":"Genetic alterations of SUGP1 mimic mutant-SF3B1 splice pattern in lung adenocarcinoma and other cancers","volume":"40","author":"Alsafadi","year":"2021","journal-title":"Oncogene"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1016\/j.molcel.2013.11.010","article-title":"RBM5, 6, and 10 differentially regulate NUMB alternative splicing to control cancer cell proliferation","volume":"52","author":"Bechara","year":"2013","journal-title":"Mol. Cell"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Lo, A., McSharry, M., and Berger, A.H. (2022). Oncogenic KRAS alters splicing factor phosphorylation and alternative splicing in lung cancer. BMC Cancer, 22.","DOI":"10.1186\/s12885-022-10311-1"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1038\/s41420-022-00820-0","article-title":"USP15 and USP4 facilitate lung cancer cell proliferation by regulating the alternative splicing of SRSF1","volume":"8","author":"Das","year":"2022","journal-title":"Cell Death Discov."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Zong, F.-Y., Fu, X., Wei, W.-J., Luo, Y.-G., Heiner, M., Cao, L.-J., Fang, Z., Fang, R., Lu, D., and Ji, H. (2014). The RNA-binding protein QKI suppresses cancer-associated aberrant splicing. PLoS Genet., 10.","DOI":"10.1371\/journal.pgen.1004289"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1007\/s10637-017-0555-8","article-title":"A phase IIa study of HA-irinotecan, formulation of hyaluronic acid and irinotecan targeting CD44 in extensive-stage small cell lung cancer","volume":"36","author":"Alamgeer","year":"2018","journal-title":"Investig. New Drugs"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"194388","DOI":"10.1016\/j.bbagrm.2019.05.006","article-title":"Alternative splicing in lung cancer","volume":"1862","author":"Coomer","year":"2019","journal-title":"Biochim. Biophys. Acta Gene Regul. Mech."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/S0304-3835(97)00254-1","article-title":"CD44 expression in metastatic and non-metastatic non-small cell lung cancers","volume":"119","author":"Kargi","year":"1997","journal-title":"Cancer Lett."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1016\/j.stem.2014.01.009","article-title":"CD44v6 is a marker of constitutive and reprogrammed cancer stem cells driving colon cancer metastasis","volume":"14","author":"Todaro","year":"2014","journal-title":"Cell Stem Cell"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1186\/s13045-018-0605-5","article-title":"The biology and role of CD44 in cancer progression: Therapeutic implications","volume":"11","author":"Chen","year":"2018","journal-title":"J. Hematol. Oncol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"111850","DOI":"10.1016\/j.yexcr.2020.111850","article-title":"CD44 variant 6 is associated with prostate cancer growth and chemo-\/radiotherapy response in vivo","volume":"388","author":"Ni","year":"2020","journal-title":"Exp. Cell Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"4185","DOI":"10.1158\/0008-5472.CAN-20-1079","article-title":"Cancer cell CD44 mediates macrophage\/monocyte-driven regulation of head and neck cancer stem cells","volume":"80","author":"Gomez","year":"2020","journal-title":"Cancer Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1016\/j.ccr.2011.01.038","article-title":"CD44 variant regulates redox status in cancer cells by stabilizing the xCT subunit of system xc\u2212 and thereby promotes tumor growth","volume":"19","author":"Ishimoto","year":"2011","journal-title":"Cancer Cell"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1002\/path.1711770406","article-title":"Standard and variant CD44 isoforms are commonly expressed in lung cancer of the non-small cell type but not of the small cell type","volume":"177","author":"Ariza","year":"1995","journal-title":"J. Pathol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1186\/s40164-020-00192-0","article-title":"CD44 as a tumor biomarker and therapeutic target","volume":"9","author":"Xu","year":"2020","journal-title":"Exp. Hematol. Oncol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.5966\/sctm.2015-0048","article-title":"Concise review: Emerging role of CD44 in cancer stem cells: A promising biomarker and therapeutic target","volume":"4","author":"Yan","year":"2015","journal-title":"Stem Cells Transl. Med."},{"key":"ref_30","first-page":"2155","article-title":"Different splicing isoforms of ERCC1 affect the expression of its overlapping genes CD3EAP and PPP1R13L, and indicate a potential application in non-small cell lung cancer treatment","volume":"52","author":"Zhang","year":"2018","journal-title":"Int. J. Oncol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1437","DOI":"10.1016\/j.molonc.2016.08.001","article-title":"A large-scale analysis of alternative splicing reveals a key role of QKI in lung cancer","volume":"10","author":"Pajares","year":"2016","journal-title":"Mol. Oncol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1186\/s12967-023-04754-8","article-title":"Altered splicing machinery in lung carcinoids unveils NOVA1, PRPF8 and SRSF10 as novel candidates to understand tumor biology and expand biomarker discovery","volume":"21","author":"Mangili","year":"2023","journal-title":"J. Transl. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1253","DOI":"10.1158\/2159-8290.CD-RW2014-198","article-title":"RBM4-regulated alternative splicing suppresses tumorigenesis","volume":"4","author":"Wang","year":"2014","journal-title":"Cancer Discov."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1056\/NEJMoa1214271","article-title":"ERCC1 Isoform Expression and DNA Repair in Non\u2013Small-Cell Lung Cancer","volume":"368","author":"Friboulet","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"13246","DOI":"10.1038\/s41598-024-63976-y","article-title":"RPS24 alternative splicing is a marker of cancer progression and epithelial\u2013mesenchymal transition","volume":"14","author":"Park","year":"2024","journal-title":"Sci. Rep."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"101374","DOI":"10.1016\/j.gendis.2024.101374","article-title":"Differences between lung adenocarcinoma and lung squamous cell carcinoma: Driver genes, therapeutic targets, and clinical efficacy","volume":"12","author":"Shen","year":"2025","journal-title":"Genes Dis."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"174171","DOI":"10.1172\/JCI174171","article-title":"Genomic insights into the mechanisms of FGFR1 dependency in squamous cell lung cancer","volume":"133","author":"Makinen","year":"2023","journal-title":"J. Clin. Investig."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"6084","DOI":"10.1158\/0008-5472.CAN-19-2132","article-title":"Epigenomic profiling discovers trans-lineage SOX2 partnerships driving tumor heterogeneity in lung squamous cell carcinoma","volume":"79","author":"Sato","year":"2019","journal-title":"Cancer Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1038\/s41392-024-01981-3","article-title":"Mechanism exploration and model construction for small cell transformation in EGFR-mutant lung adenocarcinomas","volume":"9","author":"Li","year":"2024","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1038\/s41392-024-01828-x","article-title":"Notch signaling pathway in cancer: From mechanistic insights to targeted therapies","volume":"9","author":"Shi","year":"2024","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Bao, G., Li, T., Guan, X., Yao, Y., Liang, J., Xiang, Y., and Zhong, X. (2022). Development of a prognostic alternative splicing signature associated with tumor microenvironment immune profiles in lung adenocarcinoma. Front. Oncol., 12.","DOI":"10.3389\/fonc.2022.880478"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2460","DOI":"10.1158\/1078-0432.CCR-12-3708","article-title":"Tumor-specific isoform switch of the fibroblast growth factor receptor 2 underlies the mesenchymal and malignant phenotypes of clear cell renal cell carcinomas","volume":"19","author":"Zhao","year":"2013","journal-title":"Clin. Cancer Res."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Liu, Y., Jia, W., Li, J., Zhu, H., and Yu, J. (2020). Identification of survival-associated alternative splicing signatures in lung squamous cell carcinoma. Front. Oncol., 10.","DOI":"10.3389\/fonc.2020.587343"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"10490","DOI":"10.1074\/jbc.M116.752469","article-title":"Transforming growth factor beta1 (TGF\u03b21)-induced CD44V6-NOX4 signaling in pathogenesis of idiopathic pulmonary fibrosis","volume":"292","author":"Ghatak","year":"2017","journal-title":"J. Biol. Chem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1742","DOI":"10.1158\/0008-5472.CAN-22-3184","article-title":"Genome-wide splicing quantitative expression locus analysis identifies causal risk variants for non-small cell lung cancer","volume":"83","author":"Jin","year":"2023","journal-title":"Cancer Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"102681","DOI":"10.1016\/j.omtn.2025.102681","article-title":"Transcriptomic analysis reveals lung cancer and subtype-specific alternative splicing biomarkers regulated by RNA-binding proteins","volume":"36","author":"Liu","year":"2025","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2215","DOI":"10.1016\/j.celrep.2017.08.012","article-title":"The functional impact of alternative splicing in cancer","volume":"20","author":"Godzik","year":"2017","journal-title":"Cell Rep."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1007\/s12032-021-01490-1","article-title":"Development of alternative splicing signature in lung squamous cell carcinoma","volume":"38","author":"Yan","year":"2021","journal-title":"Med. Oncol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1186\/s13073-024-01328-1","article-title":"PARP4 interacts with hnRNPM to regulate splicing during lung cancer progression","volume":"16","author":"Lee","year":"2024","journal-title":"Genome Med."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"5","DOI":"10.3892\/or.2023.8664","article-title":"U2AF1 in various neoplastic diseases and relevant targeted therapies for malignant cancers with complex mutations","volume":"51","author":"Nian","year":"2024","journal-title":"Oncol. Rep."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1661","DOI":"10.1038\/s41588-026-02648-1","article-title":"U2AF1 mutations rescue deleterious exon skipping induced by KRAS mutations","volume":"58","author":"Walter","year":"2026","journal-title":"Nat. Genet."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"e70432","DOI":"10.1002\/mco2.70432","article-title":"Separase inhibition enhances gefitinib sensitivity of lung cancer via PTBP1\/TAK1\/RIPK1-mediated PANoptosis","volume":"6","author":"Peng","year":"2025","journal-title":"MedComm"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1038\/s41419-024-06898-x","article-title":"PRMT1 promotes Warburg effect by regulating the PKM2\/PKM1 ratio in non-small cell lung cancer","volume":"15","author":"Peng","year":"2024","journal-title":"Cell Death Dis."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1186\/s12935-025-03660-x","article-title":"HNRNPC promotes progression of non-small cell lung cancer by maintaining TFAP2A mRNA stability","volume":"25","author":"Liao","year":"2025","journal-title":"Cancer Cell Int."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1016\/j.cpt.2023.04.004","article-title":"RNA splicing alterations in lung cancer pathogenesis and therapy","volume":"1","author":"Yan","year":"2023","journal-title":"Cancer Pathog. Ther."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1186\/s13059-020-02240-8","article-title":"Aberrant splicing isoforms detected by full-length transcriptome sequencing as transcripts of potential neoantigens in non-small cell lung cancer","volume":"22","author":"Oka","year":"2021","journal-title":"Genome Biol."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Hassn Mesrati, M., Syafruddin, S.E., Mohtar, M.A., and Syahir, A. (2021). CD44: A multifunctional mediator of cancer progression. Biomolecules, 11.","DOI":"10.3390\/biom11121850"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"122345","DOI":"10.1016\/j.lfs.2023.122345","article-title":"CD44s and CD44v8\u201310 isoforms confer acquired resistance to osimertinib by activating the ErbB3\/STAT3 signaling pathway","volume":"336","author":"Liu","year":"2024","journal-title":"Life Sci."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"6213","DOI":"10.1093\/nar\/gkab437","article-title":"CD44 alternative splicing senses intragenic DNA methylation in tumors via direct and indirect mechanisms","volume":"49","author":"Batsche","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Maltseva, D., and Tonevitsky, A. (2023). RNA-binding proteins regulating the CD44 alternative splicing. Front. Mol. Biosci., 10.","DOI":"10.3389\/fmolb.2023.1326148"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1186\/s13046-025-03278-x","article-title":"SNORA37\/CMTR1\/ELAVL1 feedback loop drives gastric cancer progression via facilitating CD44 alternative splicing","volume":"44","author":"Bao","year":"2025","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1038\/s41392-021-00486-7","article-title":"Alternative splicing and cancer: A systematic review","volume":"6","author":"Zhang","year":"2021","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1186\/s13073-023-01226-y","article-title":"Long-read sequencing reveals the landscape of aberrant alternative splicing and novel therapeutic target in colorectal cancer","volume":"15","author":"Sun","year":"2023","journal-title":"Genome Med."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Du, Y., Rokavec, M., and Hermeking, H. (2026). RBM47-Induced Gasdermin A\/GSDMA Mediates Mesenchymal\u2013Epithelial Transition and Pyroptosis of Colorectal Cancer Cells. Cancers, 18.","DOI":"10.3390\/cancers18030504"},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Chen, H., Tang, J., and Xiang, J. (2025). Alternative splicing in tumorigenesis and cancer therapy. Biomolecules, 15.","DOI":"10.3390\/biom15060789"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"8348","DOI":"10.1093\/nar\/gkq731","article-title":"Anti-tumor activity of splice-switching oligonucleotides","volume":"38","author":"Bauman","year":"2010","journal-title":"Nucleic Acids Res."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1038\/s41598-018-36728-y","article-title":"A VEGF-A\/SOX2\/SRSF2 network controls VEGFR1 pre-mRNA alternative splicing in lung carcinoma cells","volume":"9","author":"Gazzeri","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1093\/jmcb\/mjaa063","article-title":"QKI-5 regulates the alternative splicing of cytoskeletal gene ADD3 in lung cancer","volume":"13","author":"Wang","year":"2021","journal-title":"J. Mol. Cell Biol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"814","DOI":"10.1038\/s42003-025-08193-7","article-title":"LSM12 promotes lung squamous cell carcinoma progression through mediating alternative splicing of ARRB1","volume":"8","author":"Wu","year":"2025","journal-title":"Commun. Biol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1181","DOI":"10.1042\/BST20253091","article-title":"Mechanistic insights into MET exon 14 skipping mutations and their role in tumor progression","volume":"53","author":"Ghosh","year":"2025","journal-title":"Biochem. Soc. Trans."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1186\/s12943-025-02425-4","article-title":"Long non-coding RNA AFAP1-AS1 promotes alternative splicing of AXIN2 by facilitating SRSFs phase separation to induce drug resistance in lung adenocarcinoma","volume":"24","author":"Ouyang","year":"2025","journal-title":"Mol. Cancer"},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Luo, W., Xu, M., Wong, N., and Ng, C.S. (2025). Alternative splicing in lung adenocarcinoma: From bench to bedside. Cancers, 17.","DOI":"10.3390\/cancers17081329"},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Bonner, E.A., and Lee, S.C. (2023). Therapeutic targeting of RNA splicing in cancer. Genes, 14.","DOI":"10.3390\/genes14071378"},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"De Paoli-Iseppi, R., Gleeson, J., and Clark, M.B. (2021). Isoform age: Splice isoform profiling using long-read technologies. Front. Mol. Biosci., 8, Corrigendum in Front. Mol. Biosci. 2021, 8, 767743. https:\/\/doi.org\/10.3389\/fmolb.2021.767743.","DOI":"10.3389\/fmolb.2021.767743"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"2301","DOI":"10.1016\/j.apsb.2025.03.023","article-title":"RNA splicing: Novel star in pulmonary diseases with a treatment perspective","volume":"15","author":"Niu","year":"2025","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"56","DOI":"10.52601\/bpr.2024.240053","article-title":"Advancements in proteogenomics for preclinical targeted cancer therapy research","volume":"11","author":"Suo","year":"2025","journal-title":"Biophys. Rep."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1615","DOI":"10.1158\/1535-7163.MCT-07-2383","article-title":"DNA vaccination with CD44 variant isoform reduces mammary tumor local growth and lung metastasis","volume":"7","author":"Rubinstein","year":"2008","journal-title":"Mol. Cancer Ther."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"6955","DOI":"10.4049\/jimmunol.1004043","article-title":"CD44 reciprocally regulates the differentiation of encephalitogenic Th1\/Th17 and Th2\/regulatory T cells through epigenetic modulation involving DNA methylation of cytokine gene promoters, thereby controlling the development of experimental autoimmune encephalomyelitis","volume":"186","author":"Guan","year":"2011","journal-title":"J. Immunol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/16\/7269\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T10:41:33Z","timestamp":1786704093000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/16\/7269"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,14]]},"references-count":78,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["ijms27167269"],"URL":"https:\/\/doi.org\/10.3390\/ijms27167269","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,14]]}}}