{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T20:10:02Z","timestamp":1790799002116,"version":"4.1.0"},"reference-count":122,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Nowadays, most cancer research still depends on traditional cell culture in Petri dishes or cell culture flasks which do not have the ability to mimic physiological-like conditions in vitro. However, the behavior of cancer cells strongly relies on the interaction with their extracellular microenvironment. Consequently, current advanced approaches focus on three-dimensional (3D) cell culture to overcome such limitations and to enable a better understanding of fundamental processes including cancer development, progression, apoptosis and invasion. However, transcriptional adaptation to and temporal stability within an in vitro 3D microenvironment still appear to be remarkably understudied. In our study, we compared the cellular behavior and whole transcriptome gene expression of three frequently used non-invasive cancer cell lines (HCT-116, A549 and T47D), embedded within a collagen I (Coll I)-based 3D microenvironment to its counterparts grown as simple monolayers in a time-dependent manner. Thereby, changes in morphology and doubling time became apparent between both cultivation systems, and RNA sequencing-based transcriptome-wide analysis revealed a remarkable increase in transcriptional complexity under 3D conditions. In line with the 3D-dependent phenotype, unidirectional shifts for genes involved in cell cycle regulation (e.g., CCNB1, CCNB2), cell\u2013matrix interaction (e.g., ADAM8, ITGA2) and metabolic signaling (e.g., HK2, ENO2) were identified over time, being either activated or repressed. Interestingly, all three cell lines cultured in Coll I matrices displayed a highly distinct RNA content and composition, along with a significantly increased number of expressed protein-coding genes (increase of 3\u20136%) as well as long non-coding RNAs (increase of 26\u201348%), suggesting a more multifaceted transcription profile under 3D conditions. Our work clearly highlights that an in vitro 3D Coll I-based cell culture system has an incisive cell-specific impact on the whole transcriptome on a qualitative and quantitative level. This tremendous transcriptional reprogramming implies essential changes in gene regulatory networks and affects phenotypic cancer cell behavior, which should be considered when focusing on downstream applications.<\/jats:p>","DOI":"10.3390\/ijms27156907","type":"journal-article","created":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T12:57:56Z","timestamp":1785761876000},"page":"6907","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Adaptation of Non-Invasive Cancer Cells to 3D Collagen I Microenvironment Induces Transcriptional Reprogramming Accompanied by a More Complex RNA Landscape"],"prefix":"10.3390","volume":"27","author":[{"given":"Theresa","family":"Wie\u00dfner-Kroh","sequence":"first","affiliation":[{"name":"Research Genetic Cancer Centre (RGCC) Central Europe GmbH, Weinbergweg 22, D-06120 Halle (Saale), Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefanie","family":"H\u00fcbschmann","sequence":"additional","affiliation":[{"name":"Research Genetic Cancer Centre (RGCC) Central Europe GmbH, Weinbergweg 22, D-06120 Halle (Saale), Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3311-5096","authenticated-orcid":false,"given":"Gudrun","family":"Marquardt","sequence":"additional","affiliation":[{"name":"Research Genetic Cancer Centre (RGCC) Central Europe GmbH, Weinbergweg 22, D-06120 Halle (Saale), Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Szczesny","sequence":"additional","affiliation":[{"name":"Research Genetic Cancer Centre (RGCC) Central Europe GmbH, Weinbergweg 22, D-06120 Halle (Saale), Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miriam","family":"Faxel","sequence":"additional","affiliation":[{"name":"Research Genetic Cancer Centre (RGCC) Central Europe GmbH, Weinbergweg 22, D-06120 Halle (Saale), Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Rubner","sequence":"additional","affiliation":[{"name":"Research Genetic Cancer Centre (RGCC) Central Europe GmbH, Weinbergweg 22, D-06120 Halle (Saale), Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6145-946X","authenticated-orcid":false,"given":"Ioannis","family":"Papasotiriou","sequence":"additional","affiliation":[{"name":"Research Genetic Cancer Centre (RGCC) International GmbH, Baarerstrasse 95, CH-6300 Zug, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Langhans, S.A. (2018). Three-Dimensional In Vitro Cell Culture Models in Drug Discovery and Drug Repositioning. Front. Pharmacol., 9.","DOI":"10.3389\/fphar.2018.00006"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Habanjar, O., Diab-Assaf, M., Caldefie-Chezet, F., and Delort, L. (2021). 3D Cell Culture Systems: Tumor Application, Advantages, and Disadvantages. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222212200"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Poornima, K., Francis, A.P., Hoda, M., Eladl, M.A., Subramanian, S., Veeraraghavan, V.P., El-Sherbiny, M., Asseri, S.M., Hussamuldin, A.B.A., and Surapaneni, K.M. (2022). Implications of Three-Dimensional Cell Culture in Cancer Therapeutic Research. Front. Oncol., 12.","DOI":"10.3389\/fonc.2022.891673"},{"key":"ref_4","first-page":"3015","article-title":"Deconstructing the Third Dimension: How 3D Culture Microenvironments Alter Cellular Cues","volume":"125","author":"Baker","year":"2012","journal-title":"J. Cell Sci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1083\/jcb.201102147","article-title":"The Extracellular Matrix: A Dynamic Niche in Cancer Progression","volume":"196","author":"Lu","year":"2012","journal-title":"J. Cell Biol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2009","DOI":"10.1039\/C8BM00303C","article-title":"Biomimetic Tumor Microenvironments Based on Collagen Matrices","volume":"6","author":"Sapudom","year":"2018","journal-title":"Biomater. Sci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1038\/nrm3112","article-title":"Balancing Forces: Architectural Control of Mechanotransduction","volume":"12","author":"DuFort","year":"2011","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1038\/nrm2125","article-title":"Matrix Metalloproteinases and the Regulation of Tissue Remodelling","volume":"8","author":"Ewald","year":"2007","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"155890","DOI":"10.1016\/j.prp.2025.155890","article-title":"A Floating Collagen Matrix Triggers Ring Formation and Stemness Characteristics in Human Colorectal Cancer Organoids","volume":"269","author":"Wimmers","year":"2025","journal-title":"Pathol. Res. Pract."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1007\/s13770-025-00790-1","article-title":"Human Subcutaneous Derived Stromal Vascular Fraction Endothelial Cells Display Venous and Arterial Markers in Culture and 3D Capillaries","volume":"23","author":"Schwager","year":"2026","journal-title":"Tissue Eng. Regen. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"bio061911","DOI":"10.1242\/bio.061911","article-title":"Human Adipose Stromal Cells Differentiate towards a Tendon Phenotype with Adapted Visco-Elastic Properties in a 3D-Culture System","volume":"14","author":"Fouchard","year":"2025","journal-title":"Biol. Open"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Oliveros Anerillas, L., Kingham, P.J., Lammi, M.J., Wiberg, M., and Kelk, P. (2021). Three-Dimensional Osteogenic Differentiation of Bone Marrow Mesenchymal Stem Cells Promotes Matrix Metallopeptidase 13 (MMP13) Expression in Type I Collagen Hydrogels. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222413594"},{"key":"ref_13","first-page":"1787","article-title":"Effects of Three-Dimensional Collagen Scaffolds on the Expression Profiles and Biological Functions of Glioma Cells","volume":"52","author":"Jia","year":"2018","journal-title":"Int. J. Oncol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e03250","DOI":"10.1002\/adhm.202503250","article-title":"Spherical Skin Model: Stratified Co-Culture of Fibroblasts and Keratinocytes on Spherical Beads Toward Compound Screening","volume":"15","author":"Lenzi","year":"2026","journal-title":"Adv. Healthc. Mater."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1158","DOI":"10.1007\/s11626-025-01109-z","article-title":"Immunomodulatory Properties of Mesenchymal Stem Cells within Three-Dimensional Collagen Matrices","volume":"61","author":"Yustisia","year":"2025","journal-title":"Vitr. Cell. Dev. Biol. Anim."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"e70156","DOI":"10.1002\/jcp.70156","article-title":"Extracellular pH and NHE1 Regulate Ductal Branching Morphogenesis in Organotypic Cultures of Human Pancreatic Duct Epithelial Cells","volume":"241","author":"Molfetta","year":"2026","journal-title":"J. Cell. Physiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2559","DOI":"10.1007\/s00204-026-04324-z","article-title":"A Collagen Hydrogel\u2013Based 3D Heparg Model for Enhanced Hepatocyte Function and Assessment of Cholestatic Drug-Induced Liver Injury","volume":"100","author":"Tolosa","year":"2026","journal-title":"Arch. Toxicol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1186\/s13287-024-03971-2","article-title":"Enhancing Differentiation and Functionality of Insulin-Producing Cells Derived from iPSCs Using Esterified Collagen Hydrogel for Cell Therapy in Diabetes Mellitus","volume":"15","author":"Moon","year":"2024","journal-title":"Stem Cell Res. Ther."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"42049","DOI":"10.1038\/srep42049","article-title":"Collagen Scaffold Microenvironments Modulate Cell Lineage Commitment for Differentiation of Bone Marrow Cells into Regulatory Dendritic Cells","volume":"7","author":"Fang","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Ghosh, S., B\u00f6rsch, A., Ghosh, S., and Zavolan, M. (2021). The Transcriptional Landscape of a Hepatoma Cell Line Grown on Scaffolds of Extracellular Matrix Proteins. BMC Genom., 22.","DOI":"10.1186\/s12864-021-07532-2"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"7259","DOI":"10.1038\/s41598-021-86664-7","article-title":"Differential Reprogramming of Breast Cancer Subtypes in 3D Cultures and Implications for Sensitivity to Targeted Therapy","volume":"11","author":"Koedoot","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.molonc.2007.02.004","article-title":"The Morphologies of Breast Cancer Cell Lines in Three-Dimensional Assays Correlate with Their Profiles of Gene Expression","volume":"1","author":"Kenny","year":"2007","journal-title":"Mol. Oncol."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Luca, A.C., Mersch, S., Deenen, R., Schmidt, S., Messner, I., Sch\u00e4fer, K.-L., Baldus, S.E., Huckenbeck, W., Piekorz, R.P., and Knoefel, W.T. (2013). Impact of the 3D Microenvironment on Phenotype, Gene Expression, and EGFR Inhibition of Colorectal Cancer Cell Lines. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0059689"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"103246","DOI":"10.1016\/j.tice.2025.103246","article-title":"Three-Dimensional Cell Culture In Vitro Could Better Recapitulate the Biological Behavior of Cells In Vivo","volume":"99","author":"Qi","year":"2026","journal-title":"Tissue Cell"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Palazzo, A.F., and Lee, E.S. (2015). Non-Coding RNA: What Is Functional and What Is Junk?. Front. Genet., 6.","DOI":"10.3389\/fgene.2015.00002"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1038\/s41422-024-00975-8","article-title":"Coding, or Non-Coding, That Is the Question","volume":"34","author":"Poliseno","year":"2024","journal-title":"Cell Res."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Flores-Garc\u00eda, L.C., Rubio, K., Ibarra-Sierra, E., Silva-C\u00e1zares, M.B., Palma-Flores, C., and L\u00f3pez-Camarillo, C. (2025). Epigenetic and Transcriptional Reprogramming in 3D Culture Models in Breast Cancer. Cancers, 17.","DOI":"10.3390\/cancers17233830"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1089\/hum.2023.074","article-title":"Long Non-Coding RNAs, Cell Cycle, and Human Breast Cancer","volume":"34","author":"Yin","year":"2023","journal-title":"Hum. Gene Ther."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"176","DOI":"10.3390\/onco1020014","article-title":"Decoding the Oncogenic Signals from the Long Non-Coding RNAs","volume":"1","author":"Nadhan","year":"2021","journal-title":"Onco"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Charidemou, E., and Papaneophytou, C. (2026). Non-Coding RNAs in Cancer: Decoding Regulatory Networks for Liquid Biopsy Applications. Genes, 17.","DOI":"10.3390\/genes17040446"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Nu\u00f1ez-Olvera, S.I., Aguilar-Arnal, L., Cisneros-Villanueva, M., Hidalgo-Miranda, A., Marchat, L.A., Salinas-Vera, Y.M., Ramos-Pay\u00e1n, R., P\u00e9rez-Plasencia, C., Carlos-Reyes, \u00c1., and Puente-Rivera, J. (2022). Breast Cancer Cells Reprogram the Oncogenic lncRNAs\/mRNAs Coexpression Networks in Three-Dimensional Microenvironment. Cells, 11.","DOI":"10.3390\/cells11213458"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Jadaliha, M., Gholamalamdari, O., Tang, W., Zhang, Y., Petracovici, A., Hao, Q., Tariq, A., Kim, T.G., Holton, S.E., and Singh, D.K. (2018). A Natural Antisense lncRNA Controls Breast Cancer Progression by Promoting Tumor Suppressor Gene mRNA Stability. PLoS Genet., 14.","DOI":"10.1371\/journal.pgen.1007802"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"9138","DOI":"10.1002\/cam4.3570","article-title":"LncRNA MALAT1 Accelerates Non-small Cell Lung Cancer Progression via Regulating miR-185-5p\/MDM4 Axis","volume":"9","author":"Wang","year":"2020","journal-title":"Cancer Med."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Lovitt, C.J., Shelper, T.B., and Avery, V.M. (2018). Doxorubicin Resistance in Breast Cancer Cells Is Mediated by Extracellular Matrix Proteins. BMC Cancer, 18.","DOI":"10.1186\/s12885-017-3953-6"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"45745","DOI":"10.18632\/oncotarget.9935","article-title":"The Relevance of Using 3D Cell Cultures, in Addition to 2D Monolayer Cultures, When Evaluating Breast Cancer Drug Sensitivity and Resistance","volume":"7","author":"Breslin","year":"2016","journal-title":"Oncotarget"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Chen, S.-H., Yu, J.-H., Lin, Y.-C., Chang, Y.-M., Liu, N.-T., and Chen, S.-F. (2025). Application of an Integrated Single-Cell and Three-Dimensional Spheroid Culture Platform for Investigating Drug Resistance Heterogeneity and Epithelial\u2013Mesenchymal Transition (EMT) in Lung Cancer Subclones. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26041766"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"18380","DOI":"10.1038\/s41598-023-45144-w","article-title":"Comparative Analysis between 2D and 3D Colorectal Cancer Culture Models for Insights into Cellular Morphological and Transcriptomic Variations","volume":"13","author":"Abbas","year":"2023","journal-title":"Sci. Rep."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"bvae040","DOI":"10.1210\/jendso\/bvae040","article-title":"Transcriptome Analysis Reveals Distinct Patterns Between the Invasive and Noninvasive Pituitary Neuroendocrine Tumors","volume":"8","author":"Jotanovic","year":"2024","journal-title":"J. Endocr. Soc."},{"key":"ref_39","first-page":"203","article-title":"Comparison of Cancer Cells in 2D vs 3D Culture Reveals Differences in AKT\u2013mTOR\u2013S6K Signaling and Drug Responses","volume":"130","author":"Riedl","year":"2017","journal-title":"J. Cell Sci."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.matbio.2019.06.009","article-title":"Peptide Gels of Fully-Defined Composition and Mechanics for Probing Cell-Cell and Cell-Matrix Interactions In Vitro","volume":"85\u201386","author":"Ashworth","year":"2020","journal-title":"Matrix Biol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1038\/s42003-020-0973-6","article-title":"Cells Grown in Three-Dimensional Spheroids Mirror In Vivo Metabolic Response of Epithelial Cells","volume":"3","author":"Lagies","year":"2020","journal-title":"Commun. Biol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"19506","DOI":"10.1038\/s41598-025-03504-8","article-title":"2D versus 3D Tumor-on-Chip Models to Study the Impact of Tumor Organization on Metabolic Patterns In Vitro","volume":"15","author":"Mosseri","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"6775","DOI":"10.1038\/s41598-021-86028-1","article-title":"Morphofunctional Analysis of Human Pancreatic Cancer Cell Lines in 2- and 3-Dimensional Cultures","volume":"11","author":"Minami","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Laurent, J., Frongia, C., Cazales, M., Mondesert, O., Ducommun, B., and Lobjois, V. (2013). Multicellular Tumor Spheroid Models to Explore Cell Cycle Checkpoints in 3D. BMC Cancer, 13.","DOI":"10.1186\/1471-2407-13-73"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"14135","DOI":"10.1038\/s41598-017-14458-x","article-title":"Quantitative Label-Free Single Cell Tracking in 3D Biomimetic Matrices","volume":"7","author":"Sapudom","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"4833","DOI":"10.1016\/j.biomaterials.2009.05.043","article-title":"Control of 3-Dimensional Collagen Matrix Polymerization for Reproducible Human Mammary Fibroblast Cell Culture in Microfluidic Devices","volume":"30","author":"Sung","year":"2009","journal-title":"Biomaterials"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1242\/jcs.071985","article-title":"Integrin A5\u03b21 Facilitates Cancer Cell Invasion through Enhanced Contractile Forces","volume":"124","author":"Mierke","year":"2011","journal-title":"J. Cell Sci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1016\/j.biomaterials.2015.02.022","article-title":"The Phenotype of Cancer Cell Invasion Controlled by Fibril Diameter and Pore Size of 3D Collagen Networks","volume":"52","author":"Sapudom","year":"2015","journal-title":"Biomaterials"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"970","DOI":"10.1016\/j.identj.2024.09.035","article-title":"TPPP3, a Good Prognostic Indicator, Suppresses Cell Proliferation and Migration in OSCC","volume":"75","author":"Xiao","year":"2025","journal-title":"Int. Dent. J."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1750","DOI":"10.7150\/jca.18943","article-title":"Knockdown of Tubulin Polymerization Promoting Protein Family Member 3 Inhibits Cell Proliferation and Invasion in Human Colorectal Cancer","volume":"8","author":"Ye","year":"2017","journal-title":"J. Cancer"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"17960","DOI":"10.1038\/s41598-023-45233-w","article-title":"TPPP3 Promote Epithelial-Mesenchymal Transition via Snail1 in Glioblastoma","volume":"13","author":"Xu","year":"2023","journal-title":"Sci. Rep."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"8485","DOI":"10.1080\/21655979.2021.1984006","article-title":"Tubulin Polymerization Promoting Protein Family Member 3 (TPPP3) Overexpression Inhibits Cell Proliferation and Invasion in Nasopharyngeal Carcinoma","volume":"12","author":"Su","year":"2021","journal-title":"Bioengineered"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"341","DOI":"10.2147\/BTT.S522325","article-title":"Targeting CREBRF in Cancer: Mechanistic Insights and Future Directions","volume":"19","author":"Lv","year":"2025","journal-title":"Biol. Targets Ther."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Kumar, R., Iden, M., Tsaih, S.-W., Schmidt, R., Ojesina, A.I., and Rader, J.S. (2024). Deciphering the Divergent Transcriptomic Landscapes of Cervical Cancer Cells Grown in 3D and 2D Cell Culture Systems. Front. Cell Dev. Biol., 12.","DOI":"10.3389\/fcell.2024.1413882"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.ceb.2017.02.012","article-title":"mTORC1 Signaling and the Metabolic Control of Cell Growth","volume":"45","author":"Manning","year":"2017","journal-title":"Curr. Opin. Cell Biol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1267","DOI":"10.1016\/j.biocel.2011.05.007","article-title":"Mechanotransduction and the Regulation of mTORC1 Signaling in Skeletal Muscle","volume":"43","author":"Hornberger","year":"2011","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"114543","DOI":"10.1016\/j.celrep.2024.114543","article-title":"mTORC1 Activity Oscillates throughout the Cell Cycle, Promoting Mitotic Entry and Differentially Influencing Autophagy Induction","volume":"43","author":"Joshi","year":"2024","journal-title":"Cell Rep."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"3529","DOI":"10.1182\/blood.V120.21.3529.3529","article-title":"Polo-Like Kinase 1 (PLK1) Inhibition Reduces Cell Proliferation and Induces Apoptosis in Childhood Acute Lymphoblastic Leukemia","volume":"120","author":"Exalto","year":"2012","journal-title":"Blood"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1089\/dna.2019.5002","article-title":"PLK1 Knockdown Inhibits Cell Proliferation and Cell Apoptosis, and PLK1 Is Negatively Regulated by miR-4779 in Osteosarcoma Cells","volume":"39","author":"Zhu","year":"2020","journal-title":"DNA Cell Biol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"3149","DOI":"10.1091\/mbc.e10-05-0393","article-title":"The Roles of Cyclin A2, B1, and B2 in Early and Late Mitotic Events","volume":"21","author":"Gong","year":"2010","journal-title":"Mol. Biol. Cell"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1891","DOI":"10.1038\/s44318-025-00400-9","article-title":"PLK1 Inhibition Delays Mitotic Entry Revealing Changes to the Phosphoproteome of Mammalian Cells Early in Division","volume":"44","author":"Gobran","year":"2025","journal-title":"EMBO J."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1186\/s13046-023-02641-0","article-title":"ALDOC- and ENO2- Driven Glucose Metabolism Sustains 3D Tumor Spheroids Growth Regardless of Nutrient Environmental Conditions: A Multi-Omics Analysis","volume":"42","author":"Battaglia","year":"2023","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1080\/15384101.2015.1121354","article-title":"Cellular Microenvironment Controls the Nuclear Architecture of Breast Epithelia through \u03921-Integrin","volume":"15","author":"Bartek","year":"2016","journal-title":"Cell Cycle"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1007\/s10549-010-1013-x","article-title":"Three-Dimensional Collagen Represses Cyclin E1 via \u03921 Integrin in Invasive Breast Cancer Cells","volume":"127","author":"Wu","year":"2011","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"4869","DOI":"10.3892\/ol.2016.5369","article-title":"Biomarkers for EMT and MET in Breast Cancer: An Update","volume":"12","author":"Liu","year":"2016","journal-title":"Oncol. Lett."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"155100","DOI":"10.1016\/j.prp.2024.155100","article-title":"Malignant Phyllodes Tumor and Invasive Lobular Breast Carcinoma: Morpho-Molecular Characterization of an Uncommon Collision Tumor and Review of the Literature","volume":"254","author":"Schaumann","year":"2024","journal-title":"Pathol. Res. Pract."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1038\/s41420-025-02422-y","article-title":"Development of a Breast Cancer Invasion Score to Predict Tumor Aggressiveness and Prognosis via PI3K\/AKT\/mTOR Pathway Analysis","volume":"11","author":"Li","year":"2025","journal-title":"Cell Death Discov."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"16","DOI":"10.32604\/or.2025.068651","article-title":"CBX4 Drives Gastric Cancer Progression by Activating \u03b2-Catenin Signaling","volume":"34","author":"Jia","year":"2026","journal-title":"Oncol. Res."},{"key":"ref_69","first-page":"1","article-title":"Long-Term Cultivation Shifts Transcriptomic Profile of HCT-116 Cells","volume":"2026","author":"Marquardt","year":"2026","journal-title":"MicroPubl. Biol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"e00208","DOI":"10.1042\/BSR20150034","article-title":"3D Spheroid Cultures Improve the Metabolic Gene Expression Profiles of HepaRG Cells","volume":"35","author":"Takahashi","year":"2015","journal-title":"Biosci. Rep."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"17436","DOI":"10.1038\/s41598-025-01698-5","article-title":"LncRNA NEAT1 Regulation of the miR-101-3p\/RAC1 Axis Affects Cervical Cancer Aerobic Glycolysis and Progression","volume":"15","author":"Cao","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"e40379","DOI":"10.1097\/MD.0000000000040379","article-title":"Lnc NEAT1 Facilitates the Progression of Melanoma by Targeting the miR-152-3p\/CDK6 Axis: An Observational Study","volume":"103","author":"Ning","year":"2024","journal-title":"Medicine"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"756","DOI":"10.1186\/s12967-026-08114-0","article-title":"METTL3-Mediated m6A Modification of lncRNA MALAT1 Promotes Colorectal Cancer Progression by Activating the NF-\u03baB Signaling Pathway","volume":"24","author":"Lin","year":"2026","journal-title":"J. Transl. Med."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"e013733","DOI":"10.1136\/jitc-2025-013733","article-title":"NEAT1 Is a Therapeutic Target for Reversing T-Cell Exhaustion in Bladder Cancer","volume":"13","author":"Li","year":"2025","journal-title":"J. Immunother. Cancer"},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Anbiyaee, O., Moalemnia, A., Ghaedrahmati, F., Shooshtari, M.K., Khoshnam, S.E., Kempisty, B., Halili, S.A., Farzaneh, M., and Morenikeji, O.B. (2023). The Functions of Long Non-Coding RNA (lncRNA)-MALAT-1 in the Pathogenesis of Renal Cell Carcinoma. BMC Nephrol., 24.","DOI":"10.1186\/s12882-023-03438-1"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1186\/s11658-024-00612-7","article-title":"LncRNA TRPM2-AS Promotes Endometrial Carcinoma Progression and Angiogenesis via Targeting miR-497-5p\/SPP1 Axis","volume":"29","author":"Ma","year":"2024","journal-title":"Cell Mol. Biol. Lett."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"15330338251315625","DOI":"10.1177\/15330338251315625","article-title":"Clinical Significance and Pathogenic Mechanisms of Long Non-Coding RNA TRPM2-AS in Cancers","volume":"24","author":"Huang","year":"2025","journal-title":"Technol. Cancer Res. Treat."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"610","DOI":"10.3724\/abbs.2025082","article-title":"The lncRNA DANCR Promotes Breast Cancer Brain Metastasis by Acting as a ceRNA for miR-758-3p to Regulate PTGS2 Expression","volume":"58","author":"Li","year":"2026","journal-title":"Acta Biochim. Biophys. Sin."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1441","DOI":"10.1080\/15384101.2021.1941625","article-title":"Kr\u00fcppel-like Factor 5-Induced Overexpression of Long Non-Coding RNA DANCR Promotes the Progression of Cervical Cancer via Repressing microRNA-145-3p to Target ZEB1","volume":"20","author":"Hu","year":"2021","journal-title":"Cell Cycle"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"6970","DOI":"10.7150\/jca.44384","article-title":"The Functional Roles of Long Noncoding RNA DANCR in Human Cancers","volume":"11","author":"Pan","year":"2020","journal-title":"J. Cancer"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"4397","DOI":"10.1080\/21655979.2022.2033412","article-title":"Long Non-Coding RNA TRPM2 Antisense RNA as a Potential Therapeutic Target Promotes Tumorigenesis and Metastasis in Esophageal Cancer","volume":"13","author":"Wang","year":"2022","journal-title":"Bioengineered"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"e70042","DOI":"10.1002\/iub.70042","article-title":"Cannabidiol Suppresses EMT in Pancreatic Cancer via Inhibition of MALAT1 lncRNA and PI3K\/Akt\/mTOR Signaling Pathway","volume":"77","author":"Kim","year":"2025","journal-title":"IUBMB Life"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"5673","DOI":"10.1038\/s41598-025-90416-2","article-title":"Long Non-Coding RNA NEAT1 Promotes Colorectal Cancer Progression via Interacting with SIRT1","volume":"15","author":"Li","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1186\/s12935-020-01182-2","article-title":"Long Non-Coding RNA NEAT1\/miR-338-3p Axis Impedes the Progression of Acute Myeloid Leukemia via Regulating CREBRF","volume":"20","author":"Feng","year":"2020","journal-title":"Cancer Cell Int."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1101\/gad.284661.116","article-title":"Neat1 Is a P53-Inducible lincRNA Essential for Transformation Suppression","volume":"31","author":"Mello","year":"2017","journal-title":"Genes Dev."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"e2123","DOI":"10.1038\/cddis.2015.407","article-title":"Tumor-Suppressive Function of Long Noncoding RNA MALAT1 in Glioma Cells by Downregulation of MMP2 and Inactivation of ERK\/MAPK Signaling","volume":"7","author":"Han","year":"2016","journal-title":"Cell Death Dis."},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Chen, Q., Zhu, C., and Jin, Y. (2020). The Oncogenic and Tumor Suppressive Functions of the Long Noncoding RNA MALAT1: An Emerging Controversy. Front. Genet., 11.","DOI":"10.3389\/fgene.2020.00093"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1705","DOI":"10.1038\/s41588-018-0252-3","article-title":"Long Noncoding RNA MALAT1 Suppresses Breast Cancer Metastasis","volume":"50","author":"Kim","year":"2018","journal-title":"Nat. Genet."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"6451","DOI":"10.1016\/j.cell.2024.10.024","article-title":"Small and Long Non-Coding RNAs: Past, Present, and Future","volume":"187","author":"Chen","year":"2024","journal-title":"Cell"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"2380","DOI":"10.1016\/j.cmet.2021.11.011","article-title":"NEAT1 Is Essential for Metabolic Changes That Promote Breast Cancer Growth and Metastasis","volume":"33","author":"Park","year":"2021","journal-title":"Cell Metab."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"2480","DOI":"10.1158\/0008-5472.CAN-18-1432","article-title":"Long Noncoding RNA MALAT1 Regulates Cancer Glucose Metabolism by Enhancing mTOR-Mediated Translation of TCF7L2","volume":"79","author":"Malakar","year":"2019","journal-title":"Cancer Res."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1186\/s12943-025-02415-6","article-title":"MALAT1 as a Molecular Driver of Tumor Progression, Immune Evasion, and Resistance to Therapy","volume":"24","author":"Bitaraf","year":"2025","journal-title":"Mol. Cancer"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.1007\/s10495-023-01846-0","article-title":"IGF2BP2 Promotes lncRNA DANCR Stability Mediated Glycolysis and Affects the Progression of FLT3-ITD + Acute Myeloid Leukemia","volume":"28","author":"Wu","year":"2023","journal-title":"Apoptosis"},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"Yang, R., Han, S., Clayton, J., Haghighatian, M., Tsai, C.-C., Yao, Y., Li, P., Shen, J., and Zhou, Q. (2022). A Proof-of-Concept Inhibitor of Endothelial Lipase Suppresses Triple-Negative Breast Cancer Cells by Hijacking the Mitochondrial Function. Cancers, 14.","DOI":"10.3390\/cancers14153763"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"154887","DOI":"10.1016\/j.prp.2023.154887","article-title":"Contribution and Underlying Mechanisms of lncRNA TRPM2-AS in the Development and Progression of Human Cancers","volume":"251","author":"Li","year":"2023","journal-title":"Pathol. Res. Pract."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1177\/1535370218760774","article-title":"The Long Non-Coding RNA NEAT1 Contributes to Extracellular Matrix Degradation in Degenerative Human Nucleus Pulposus Cells","volume":"243","author":"Ruan","year":"2018","journal-title":"Exp. Biol. Med."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1186\/s12935-019-1016-6","article-title":"LncRNA DANCR Promotes the Proliferation, Migration, and Invasion of Tongue Squamous Cell Carcinoma Cells through miR-135a-5p\/KLF8 Axis","volume":"19","author":"Zheng","year":"2019","journal-title":"Cancer Cell Int."},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Hussein, M.A., Valinezhad, K., Adel, E., and Munirathinam, G. (2024). MALAT-1 Is a Key Regulator of Epithelial\u2013Mesenchymal Transition in Cancer: A Potential Therapeutic Target for Metastasis. Cancers, 16.","DOI":"10.3390\/cancers16010234"},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Zhao, Q., Van Der Pluijm, L., Peled, D., De Klerk, J.A., Slieker, R., T Hart, L.M., Stam, W., Duijs, J., Koudijs, A., and Rotmans, J.I. (2025). Targeting Long Noncoding RNA MALAT1 Preserves Endothelial Cell Integrity and Protects against Kidney Fibrosis. Mol. Ther. Nucleic Acids, 36.","DOI":"10.1016\/j.omtn.2025.102689"},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Lu, C., Wei, D., Zhang, Y., Wang, P., and Zhang, W. (2021). Long Non-Coding RNAs as Potential Diagnostic and Prognostic Biomarkers in Breast Cancer: Progress and Prospects. Front. Oncol., 11.","DOI":"10.3389\/fonc.2021.710538"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1654","DOI":"10.1091\/mbc.E20-02-0097","article-title":"Matrix Stiffness-Sensitive Long Noncoding RNA NEAT1 Seeded Paraspeckles in Cancer Cells","volume":"31","author":"Todorovski","year":"2020","journal-title":"Mol. Biol. Cell"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"1449","DOI":"10.3892\/mmr.2020.11196","article-title":"lncRNA MALAT1 Modulates Cancer Stem Cell Properties of Liver Cancer Cells by Regulating YAP1 Expression via miR-375 Sponging","volume":"22","author":"Zhao","year":"2020","journal-title":"Mol. Med. Rep."},{"key":"ref_103","doi-asserted-by":"crossref","unstructured":"Koyama, S., Tsuchiya, H., Amisaki, M., Sakaguchi, H., Honjo, S., Fujiwara, Y., and Shiota, G. (2020). NEAT1 Is Required for the Expression of the Liver Cancer Stem Cell Marker CD44. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21061927"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"e2404146121","DOI":"10.1073\/pnas.2404146121","article-title":"Matrix Stiffness-Dependent Regulation of Immunomodulatory Genes in Human MSCs Is Associated with the lncRNA CYTOR","volume":"121","author":"Lim","year":"2024","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"24885","DOI":"10.1038\/s41598-025-08070-7","article-title":"LncRNA DRAIC Facilitates the Progression of Renal Cell Carcinoma by Modulting the microRNA-145-3p\/ABRACL Pathway Signaling","volume":"15","author":"Wei","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"1623","DOI":"10.1158\/1541-7786.MCR-22-0123","article-title":"Functional Characterization of lncRNA152 as an Angiogenesis-Inhibiting Tumor Suppressor in Triple-Negative Breast Cancers","volume":"20","author":"Kim","year":"2022","journal-title":"Mol. Cancer Res."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"318","DOI":"10.3892\/or.2015.4364","article-title":"Upregulation of Long Non-Coding RNA PRNCR1 in Colorectal Cancer Promotes Cell Proliferation and Cell Cycle Progression","volume":"35","author":"Yang","year":"2016","journal-title":"Oncol. Rep."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"BSR20193153","DOI":"10.1042\/BSR20193153","article-title":"Long Non-Coding RNA PRNCR1 Modulates Non-Small Cell Lung Cancer Cell Proliferation, Apoptosis, Migration, Invasion, and EMT through PRNCR1\/miR-126-5p\/MTDH Axis","volume":"40","author":"Guo","year":"2020","journal-title":"Biosci. Rep."},{"key":"ref_109","first-page":"4547","article-title":"Long Non-coding RNA PRNCR1 Has an Oncogenic Role in Breast Cancer","volume":"18","author":"Guo","year":"2019","journal-title":"Exp. Ther. Med."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"5124","DOI":"10.1002\/cam4.5263","article-title":"Long Noncoding RNA HULC Regulates the NF-\u03baB Pathway and Represents a Promising Prognostic Biomarker in Liver Cancer","volume":"12","author":"Liu","year":"2023","journal-title":"Cancer Med."},{"key":"ref_111","doi-asserted-by":"crossref","unstructured":"Sapudom, J., Mohamed, W.K.E., Garcia-Sabat\u00e9, A., Alatoom, A., Karaman, S., Mahtani, N., and Teo, J.C.M. (2020). Collagen Fibril Density Modulates Macrophage Activation and Cellular Functions during Tissue Repair. Bioengineering, 7.","DOI":"10.3390\/bioengineering7020033"},{"key":"ref_112","doi-asserted-by":"crossref","unstructured":"Jiang, H., Lei, R., Ding, S.-W., and Zhu, S. (2014). Skewer: A Fast and Accurate Adapter Trimmer for next-Generation Sequencing Paired-End Reads. BMC Bioinform., 15.","DOI":"10.1186\/1471-2105-15-182"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1038\/nbt.3820","article-title":"Nextflow Enables Reproducible Computational Workflows","volume":"35","author":"Chatzou","year":"2017","journal-title":"Nat. Biotechnol."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1038\/nmeth.3317","article-title":"HISAT: A Fast Spliced Aligner with Low Memory Requirements","volume":"12","author":"Kim","year":"2015","journal-title":"Nat. Methods"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"giab008","DOI":"10.1093\/gigascience\/giab008","article-title":"Twelve Years of SAMtools and BCFtools","volume":"10","author":"Danecek","year":"2021","journal-title":"Gigascience"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"2943","DOI":"10.1093\/bioinformatics\/btac166","article-title":"Analysing High-Throughput Sequencing Data in Python with HTSeq 2.0","volume":"38","author":"Putri","year":"2022","journal-title":"Bioinformatics"},{"key":"ref_117","unstructured":"R Core Team (2014). R: A Language and Environment for Statistical Computing, R Foundation for Statistical Computing."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","article-title":"Moderated Estimation of Fold Change and Dispersion for RNA-Seq Data with DESeq2","volume":"15","author":"Love","year":"2014","journal-title":"Genome Biol."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1111\/j.2517-6161.1995.tb02031.x","article-title":"Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing","volume":"57","author":"Benjamini","year":"1995","journal-title":"J. R. Stat. Soc. Ser. B (Methodol.)"},{"key":"ref_120","unstructured":"Korotkevich, G., Sukhov, V., Budin, N., Shpak, B., Artyomov, M.N., and Sergushichev, A. (2021). Fast Gene Set Enrichment Analysis. bioRxiv, 060012."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/j.cels.2015.12.004","article-title":"The Molecular Signatures Database (MSigDB) Hallmark Gene Set Collection","volume":"1","author":"Liberzon","year":"2015","journal-title":"Cell Syst."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"15545","DOI":"10.1073\/pnas.0506580102","article-title":"Gene Set Enrichment Analysis: A Knowledge-Based Approach for Interpreting Genome-Wide Expression Profiles","volume":"102","author":"Subramanian","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/15\/6907\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T13:04:02Z","timestamp":1785762242000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/15\/6907"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,1]]},"references-count":122,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["ijms27156907"],"URL":"https:\/\/doi.org\/10.3390\/ijms27156907","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,1]]}}}