The Role of Non-Coding RNAs in Chemoresistance to Cancer Therapies
DOI:
https://doi.org/10.54133/ajms.v11i2.3214Keywords:
Cancer therapy, circRNAs, Drug resistance, lncRNAs, miRNAs, Non-coding RNAsAbstract
Chemoresistance remains one of the greatest challenges in modern oncology and is responsible for most cancer-related deaths. Growing evidence has identified non-coding RNAs (ncRNAs) as key regulators of resistance to anticancer therapy. These molecules influence a wide range of classical resistance mechanisms, including drug efflux, apoptosis evasion, epithelial–mesenchymal transition, enhanced DNA repair, altered drug metabolism, and autophagy. The growing understanding of ncRNA biology has created new opportunities for clinical translation. Non-coding RNAs show considerable promise as predictive biomarkers of treatment response and as therapeutic targets, several of which have already entered early-phase clinical evaluation. Nevertheless, significant challenges remain, including efficient and selective delivery, off-target effects, tumor heterogeneity, and redundancy in ncRNA regulatory networks.
Downloads
References
Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024;74(3):229–263. doi: 10.3322/caac.21834. DOI: https://doi.org/10.3322/caac.21834
Chen S, Cao Z, Prettner K, Kuhn M, Yang J, Jiao L, et al. Estimates and projections of the global economic cost of 29 cancers in 204 countries and territories from 2020 to 2050. JAMA Oncol. 2023;9(4):465. doi: 10.1001/jamaoncol.2022.7826. DOI: https://doi.org/10.1001/jamaoncol.2022.7826
DeVita VT, Chu E. A history of cancer chemotherapy. Cancer Res. 2008;68(21):8643–8653. doi: 10.1158/0008-5472.can-07-6611. DOI: https://doi.org/10.1158/0008-5472.CAN-07-6611
Anand U, Dey A, Chandel AKS, Sanyal R, Mishra A, Pandey DK, et al. Cancer chemotherapy and beyond: Current status, drug candidates, associated risks and progress in targeted therapeutics. Genes Dis. 2023;10(4):1367–1401. doi: 10.1016/j.gendis.2022.02.007. DOI: https://doi.org/10.1016/j.gendis.2022.02.007
Zhang WY, Yang LY, Fan XX. CAR-T therapy-based innovations in the enhancement of contemporary anti-tumor therapies. Front Immunol. 2025;16. doi: 10.3389/fimmu.2025.1622433. DOI: https://doi.org/10.3389/fimmu.2025.1622433
Kale E, Guzes E, Alatas F, Sharafi P. Next-generation cancer therapies: translating experimental advances into clinical practice. Postgrad Med J. 2026;102(1208):497–510. doi: 10.1093/postmj/qgaf242. DOI: https://doi.org/10.1093/postmj/qgaf242
Tfayli AH, El‐Halabi LN, Khuri FR. Global disparities in cancer care: Bridging the gap in affordability and access to medications between high and low‐income countries. Cancer. 2024;131(1). doi: 10.1002/cncr.35590. DOI: https://doi.org/10.1002/cncr.35590
Hofmarcher T, Charalambous A, Normanno N, Szmytke E, Wilking N. Access to novel cancer medicines in Europe: inequities across countries and their drivers. ESMO Open. 2025;10(10):105810. doi: 10.1016/j.esmoop.2025.105810. DOI: https://doi.org/10.1016/j.esmoop.2025.105810
Ruge L, Verheyen M, John F, Wolf J. Global disparities in access to diagnostics and therapies for advanced non-small cell lung cancer: from discovery to delivery – a review. Front Oncol. 2026;16. doi: 10.3389/fonc.2026.1807704. DOI: https://doi.org/10.3389/fonc.2026.1807704
Rezayatmand H, Razmkhah M, Razeghian-Jahromi I. Drug resistance in cancer therapy: the Pandora’s Box of cancer stem cells. Stem Cell Res Ther. 2022;13(1). doi: 10.1186/s13287-022-02856-6. DOI: https://doi.org/10.1186/s13287-022-02856-6
Dhiman VK, Kumari M, Singh D. Chemoresistance: The hidden barrier in cancer treatment. Cancer Pathogenesis Ther. 2026;4(2):98–109. doi: 10.1016/j.cpt.2025.07.001. DOI: https://doi.org/10.1016/j.cpt.2025.07.001
Cetin R, Quandt E, Kaulich M. Functional genomics approaches to elucidate vulnerabilities of intrinsic and acquired chemotherapy resistance. Cells. 2021;10(2):260. doi: 10.3390/cells10020260. DOI: https://doi.org/10.3390/cells10020260
Wang Q, Shen X, Chen G, Du J. Drug resistance in colorectal cancer: From mechanism to clinic. Cancers (Basel). 2022;14(12):2928. doi: 10.3390/cancers14122928. DOI: https://doi.org/10.3390/cancers14122928
Mo J, Zaremba A, Inderjeeth AJ, el Zeinaty P, Li A, Wicky A, et al. Clinical outcomes and management following progressive disease with anti-PD-(L)1 therapy in patients with advanced Merkel Cell Carcinoma. Eur J Cancer. 2025;217:115254. doi: 10.1016/j.ejca.2025.115254. DOI: https://doi.org/10.1016/j.ejca.2025.115254
Sun D, Bo L, Jiang C, Lan Y, Zhang B, Zhang C, et al. Beyond the boundary: The emerging roles of ATP-binding cassette transporters in multidrug resistance (MDR) and therapeutic targeting in cancer. Drug Resist Updates. 2026;84:101310. doi: 10.1016/j.drup.2025.101310. DOI: https://doi.org/10.1016/j.drup.2025.101310
Fulda S. Evasion of apoptosis as a cellular stress response in cancer. Int J Cell Biol. 2010;2010:1–6. doi: 10.1155/2010/370835. DOI: https://doi.org/10.1155/2010/370835
Dart A. EMT in chemoresistance. Nat Rev Cancer. 2023;23(6):349–349. doi: 10.1038/s41568-023-00581-7. DOI: https://doi.org/10.1038/s41568-023-00581-7
Nesic K, Parker P, Swisher EM, Krais JJ. DNA repair and the contribution to chemotherapy resistance. Genome Med. 2025;17(1). doi: 10.1186/s13073-025-01488-8. DOI: https://doi.org/10.1186/s13073-025-01488-8
Chen X, Chen S, Yu D. Metabolic reprogramming of chemoresistant cancer cells and the potential significance of metabolic regulation in the reversal of cancer chemoresistance. Metabolites. 2020;10(7):289. doi: 10.3390/metabo10070289. DOI: https://doi.org/10.3390/metabo10070289
Li X, Zhou Y, Li Y, Yang L, Ma Y, Peng X, et al. Autophagy: A novel mechanism of chemoresistance in cancers. Biomed Pharmacother. 2019;119:109415. doi: 10.1016/j.biopha.2019.109415. DOI: https://doi.org/10.1016/j.biopha.2019.109415
Zhou X, Ao X, Jia Z, Li Y, Kuang S, Du C, et al. Non-coding RNA in cancer drug resistance: Underlying mechanisms and clinical applications. Front Oncol. 2022;12. doi: 10.3389/fonc.2022.951864. DOI: https://doi.org/10.3389/fonc.2022.951864
Bartel DP. MicroRNAs. Cell. 2004;116(2):281–297. doi: 10.1016/s0092-8674(04)00045-5. DOI: https://doi.org/10.1016/S0092-8674(04)00045-5
Peng Y, Croce CM. The role of MicroRNAs in human cancer. Signal Transduct Target Ther. 2016;1(1). doi: 10.1038/sigtrans.2015.4. DOI: https://doi.org/10.1038/sigtrans.2015.4
Dexheimer PJ, Cochella L. MicroRNAs: From mechanism to organism. Front Cell Dev Biol. 2020;8. doi: 10.3389/fcell.2020.00409. DOI: https://doi.org/10.3389/fcell.2020.00409
Han J, Lee Y, Yeom KH, Kim YK, Jin H, Kim VN. The Drosha-DGCR8 complex in primary microRNA processing. Genes Dev. 2004;18(24):3016–3027. doi: 10.1101/gad.1262504. DOI: https://doi.org/10.1101/gad.1262504
Vergani-Junior CA, Tonon-da-Silva G, Inan MD, Mori MA. DICER: structure, function, and regulation. Biophys Rev. 2021;13(6):1081–1090. doi: 10.1007/s12551-021-00902-w. DOI: https://doi.org/10.1007/s12551-021-00902-w
Dueck A, Ziegler C, Eichner A, Berezikov E, Meister G. microRNAs associated with the different human Argonaute proteins. Nucleic Acids Res. 2012;40(19):9850–9862. doi: 10.1093/nar/gks705. DOI: https://doi.org/10.1093/nar/gks705
Pekarek L, Torres-Carranza D, Fraile-Martinez O, García-Montero C, Pekarek T, Saez MA, et al. An overview of the role of microRNAs on carcinogenesis: A focus on cell cycle, angiogenesis and metastasis. Int J Mol Sci. 2023;24(8):7268. doi: 10.3390/ijms24087268. DOI: https://doi.org/10.3390/ijms24087268
Ding S, Wang P. The life of microRNAs: Biogenesis, function and decay in cancer. Biomolecules. 2025;15(10):1393. doi: 10.3390/biom15101393. DOI: https://doi.org/10.3390/biom15101393
Dragomir MP, Knutsen E, Calin GA. Classical and noncanonical functions of miRNAs in cancers. Trend Genet. 2022;38(4):379–394. doi: 10.1016/j.tig.2021.10.002. DOI: https://doi.org/10.1016/j.tig.2021.10.002
Conn VM, Chinnaiyan AM, Conn SJ. Circular RNA in cancer. Nat Rev Cancer. 2024;24(9):597–613. doi: 10.1038/s41568-024-00721-7. DOI: https://doi.org/10.1038/s41568-024-00721-7
Hussen BM, Abdullah SR, Jaafar RM, Rasul MF, Aroutiounian R, Harutyunyan T, et al. Circular RNAs as key regulators in cancer hallmarks: New progress and therapeutic opportunities. Crit Rev Oncol Hematol. 2025;207:104612. doi: 10.1016/j.critrevonc.2024.104612. DOI: https://doi.org/10.1016/j.critrevonc.2024.104612
Guo Y, Huang Q, Heng Y, Zhou Y, Chen H, Xu C, et al. Circular RNAs in cancer. MedComm (Beijing). 2025;6(2). doi: 10.1002/mco2.70079. DOI: https://doi.org/10.1002/mco2.70079
Shafaghat Z, Radmehr S, Saharkhiz S, Khosrozadeh A, Feiz K, Alkhathami AG, et al. Circular RNA, a molecule with potential chemistry and applications in RNA-based cancer therapeutics: An insight into recent advances. Top Curr Chem. 2025;383(2). doi: 10.1007/s41061-025-00505-z. DOI: https://doi.org/10.1007/s41061-025-00505-z
Kumar L, Shamsuzzama, Haque R, Baghel T, Nazir A. Circular RNAs: The emerging class of non-coding RNAs and their potential role in human neurodegenerative diseases. Mol Neurobiol. 2016;54(9):7224–7234. doi: 10.1007/s12035-016-0213-8. DOI: https://doi.org/10.1007/s12035-016-0213-8
Sakshi S, Jayasuriya R, Ganesan K, Xu B, Ramkumar KM. Role of circRNA-miRNA-mRNA interaction network in diabetes and its associated complications. Mol Ther Nucleic Acids. 2021;26:1291–302. doi: 10.1016/j.omtn.2021.11.007. DOI: https://doi.org/10.1016/j.omtn.2021.11.007
Guo Z, Cao Q, Zhao Z, Song C. Biogenesis, features, functions, and disease relationships of a specific circular RNA: CDR1as. Aging Dis. 2020;11(4):1009. doi: 10.14336/ad.2019.0920. DOI: https://doi.org/10.14336/AD.2019.0920
Chen J, Yang J, Fei X, Wang X, Wang K. CircRNA ciRS-7: A novel oncogene in multiple cancers. Int J Biol Sci. 2021;17(1):379–3789. doi: 10.7150/ijbs.54292. DOI: https://doi.org/10.7150/ijbs.54292
Holdt LM, Stahringer A, Sass K, Pichler G, Kulak NA, Wilfert W, et al. Circular non-coding RNA ANRIL modulates ribosomal RNA maturation and atherosclerosis in humans. Nat Commun. 2016;7(1). doi: 10.1038/ncomms12429. DOI: https://doi.org/10.1038/ncomms12429
He L, Man C, Xiang S, Yao L, Wang X, Fan Y. Circular RNAs’ cap-independent translation protein and its roles in carcinomas. Mol Cancer. 2021;20(1). doi: 10.1186/s12943-021-01417-4. DOI: https://doi.org/10.1186/s12943-021-01417-4
Zhou WY, Cai ZR, Liu J, Wang DS, Ju HQ, Xu RH. Circular RNA: metabolism, functions and interactions with proteins. Mol Cancer. 2020;19(1). doi: 10.1186/s12943-020-01286-3. DOI: https://doi.org/10.1186/s12943-020-01286-3
Hashemi M, Khosroshahi EM, Daneii P, Hassanpoor A, Eslami M, Koohpar ZK, et al. Emerging roles of CircRNA-miRNA networks in cancer development and therapeutic response. Noncoding RNA Res. 2025;10:98–115. doi: 10.1016/j.ncrna.2024.09.006. DOI: https://doi.org/10.1016/j.ncrna.2024.09.006
Mattick JS, Amaral PP, Carninci P, Carpenter S, Chang HY, Chen LL, et al. Long non-coding RNAs: definitions, functions, challenges and recommendations. Nat Rev Mol Cell Biol. 2023;24(6):430–447. doi: 10.1038/s41580-022-00566-8. DOI: https://doi.org/10.1038/s41580-022-00566-8
Zhang X, Wang W, Zhu W, Dong J, Cheng Y, Yin Z, et al. Mechanisms and functions of long non-coding RNAs at multiple regulatory levels. Int J Mol Sci. 2019;20(22):5573. doi: 10.3390/ijms20225573. DOI: https://doi.org/10.3390/ijms20225573
Hu G, Niu F, Humburg BA, Liao K, Bendi S, Callen S, et al. Molecular mechanisms of long noncoding RNAs and their role in disease pathogenesis. Oncotarget. 2018;9(26):18648–18663. doi: 10.18632/oncotarget.24307. DOI: https://doi.org/10.18632/oncotarget.24307
Noh JH, Kim KM, McClusky WG, Abdelmohsen K, Gorospe M. Cytoplasmic functions of long noncoding RNAs. WIREs RNA. 2018;9(3). doi: 10.1002/wrna.1471. DOI: https://doi.org/10.1002/wrna.1471
Begicevic RR, Falasca M. ABC Transporters in cancer stem cells: Beyond chemoresistance. Int J Mol Sci. 2017;18(11):2362. doi: 10.3390/ijms18112362. DOI: https://doi.org/10.3390/ijms18112362
Huang J, Ecker GF. A structure-based view on ABC-transporter linked to multidrug resistance. Molecules. 2023;28(2):495. doi: 10.3390/molecules28020495. DOI: https://doi.org/10.3390/molecules28020495
Ebrahimnezhad M, Asl SH, Rezaie M, Molavand M, Yousefi B, Majidinia M. lncRNAs: New players of cancer drug resistance via targeting ABC transporters. IUBMB Life. 2024;76(11):883–921. doi: 10.1002/iub.2888. DOI: https://doi.org/10.1002/iub.2888
Haenisch S, Werk AN, Cascorbi I. MicroRNAs and their relevance to ABC transporters. Br J Clin Pharmacol. 2014;77(4):587–596. doi: 10.1111/bcp.12251. DOI: https://doi.org/10.1111/bcp.12251
Zhu H, Wu H, Liu X, Evans BR, Medina DJ, Liu CG, et al. Role of microRNA miR-27a and miR-451 in the regulation of MDR1/p-glycoprotein expression in human cancer cells. Biochem Pharmacol. 2008;76(5):582–588. doi: 10.1016/j.bcp.2008.06.007. DOI: https://doi.org/10.1016/j.bcp.2008.06.007
Li G, Gong J, Cao S, Wu Z, Cheng D, Zhu J, et al. The non-coding RNAs inducing drug resistance in ovarian cancer: A new perspective for understanding drug resistance. Front Oncol. 2021;11. doi: 10.3389/fonc.2021.742149. DOI: https://doi.org/10.3389/fonc.2021.742149
Ghafouri-Fard S, Shoorei H, Abak A, Abbas Raza SH, Pichler M, Taheri M. Role of non-coding RNAs in modulating the response of cancer cells to paclitaxel treatment. Biomed Pharmacother. 2021;134:111172. doi: 10.1016/j.biopha.2020.111172. DOI: https://doi.org/10.1016/j.biopha.2020.111172
Gao M, Miao L, Liu M, Li C, Yu C, Yan H, et al. miR-145 sensitizes breast cancer to doxorubicin by targeting multidrug resistance-associated protein-1. Oncotarget. 2016;7(37):59714–59726. doi: 10.18632/oncotarget.10845. DOI: https://doi.org/10.18632/oncotarget.10845
Bendoraite A, Knouf EC, Garg KS, Parkin RK, Kroh EM, O’Briant KC, et al. Regulation of miR-200 family microRNAs and ZEB transcription factors in ovarian cancer: Evidence supporting a mesothelial-to-epithelial transition. Gynecol Oncol. 2010;116(1):117–125. doi: 10.1016/j.ygyno.2009.08.009. DOI: https://doi.org/10.1016/j.ygyno.2009.08.009
Cittelly DM, Dimitrova I, Howe EN, Cochrane DR, Jean A, Spoelstra NS, et al. Restoration of miR-200c to ovarian cancer reduces tumor burden and increases sensitivity to paclitaxel. Mol Cancer Ther. 2012;11(12):2556–2565. doi: 10.1158/1535-7163.mct-12-0463. DOI: https://doi.org/10.1158/1535-7163.MCT-12-0463
Chawra HS, Agarwal M, Mishra A, Chandel SS, Singh RP, Dubey G, et al. MicroRNA-21’s role in PTEN suppression and PI3K/AKT activation: Implications for cancer biology. Pathol Res Pract. 2024;254:155091. doi: 10.1016/j.prp.2024.155091. DOI: https://doi.org/10.1016/j.prp.2024.155091
Ghafouri-Fard S, Khoshbakht T, Taheri M, Jamali E. A concise review on the role of circPVT1 in tumorigenesis, drug sensitivity, and cancer prognosis. Front Oncol. 2021;11. doi: 10.3389/fonc.2021.762960. DOI: https://doi.org/10.3389/fonc.2021.762960
Zhang X, Luo M, Zhang J, Guo B, Singh S, Lin X, et al. The role of lncRNA H19 in tumorigenesis and drug resistance of human cancers. Front Genet. 2022;13. doi: 10.3389/fgene.2022.1005522. DOI: https://doi.org/10.3389/fgene.2022.1005522
Al-Janabi II. Manipulating Cell Death in Cancer. Al-Rafidain J Med Sci. 2025;9(1):63–73. doi: 10.54133/ajms.v9i1.2131. DOI: https://doi.org/10.54133/ajms.v9i1.2131
Villanova L, Careccia S, de Maria R, Fiori M. Micro-economics of apoptosis in cancer: ncRNAs modulation of BCL-2 family members. Int J Mol Sci. 2018;19(4):958. doi: 10.3390/ijms19040958. DOI: https://doi.org/10.3390/ijms19040958
Svoronos AA, Engelman DM, Slack FJ. OncomiR or tumor suppressor? The duplicity of microRNAs in cancer. Cancer Res. 2016;76(13):3666–3670. doi: 10.1158/0008-5472.can-16-0359. DOI: https://doi.org/10.1158/0008-5472.CAN-16-0359
Rahmati Y, Asemani Y, Aghamiri S, Ezzatifar F, Najafi S. CiRS-7/CDR1as; An oncogenic circular RNA as a potential cancer biomarker. Pathol Res Pract. 2021;227:153639. doi: 10.1016/j.prp.2021.153639. DOI: https://doi.org/10.1016/j.prp.2021.153639
Hou J, Zhang G, Wang X, Wang Y, Wang K. Functions and mechanisms of lncRNA MALAT1 in cancer chemotherapy resistance. Biomark Res. 2023;11(1). doi: 10.1186/s40364-023-00467-8. DOI: https://doi.org/10.1186/s40364-023-00467-8
Ribatti D, Tamma R, Annese T. Epithelial-mesenchymal transition in cancer: A historical overview. Transl Oncol. 2020;13(6):100773. doi: 10.1016/j.tranon.2020.100773. DOI: https://doi.org/10.1016/j.tranon.2020.100773
Al-Janabi I. Epithelial-mesenchymal transition and tumour progression: An overview. Al-Rafidain J Med Sci. 2023;4:6–21. doi: 10.54133/ajms.v4i.99. DOI: https://doi.org/10.54133/ajms.v4i.99
Du B, Shim J. Targeting epithelial–mesenchymal transition (EMT) to overcome drug resistance in cancer. Molecules. 2016;21(7):965. doi: 10.3390/molecules21070965. DOI: https://doi.org/10.3390/molecules21070965
Ghorbian S. Cancer cell plasticity and therapeutic resistance: mechanisms, crosstalk, and translational perspectives. Hereditas. 2025;162(1). doi: 10.1186/s41065-025-00564-8. DOI: https://doi.org/10.1186/s41065-025-00564-8
Korpal M, Kang Y. The emerging role of miR-200 family of MicroRNAs in epithelial-mesenchymal transition and cancer metastasis. RNA Biol. 2008;5(3):115–119. doi: 10.4161/rna.5.3.6558. DOI: https://doi.org/10.4161/rna.5.3.6558
Liu J, Du H, Shi Y. Role and underlying mechanisms of miR 200 family in breast cancer (Review). Int J Oncol. 2026;68(4):1–18. doi: 10.3892/ijo.2026.5856. DOI: https://doi.org/10.3892/ijo.2026.5856
Ashrafizadeh M, Ang HL, Moghadam ER, Mohammadi S, Zarrin V, Hushmandi K, et al. MicroRNAs and their influence on the ZEB family: Mechanistic aspects and therapeutic applications in cancer therapy. Biomolecules. 2020;10(7):1040. doi: 10.3390/biom10071040. DOI: https://doi.org/10.3390/biom10071040
Matuszyk J. Circular RNA MALAT1 as a potential target for antimetastatic therapy. Noncoding RNA Res. 2026;17:12–20. doi: 10.1016/j.ncrna.2025.11.004. DOI: https://doi.org/10.1016/j.ncrna.2025.11.004
Hussein MA, Valinezhad K, Adel E, Munirathinam G. MALAT-1 is a key regulator of epithelial–mesenchymal transition in cancer: A potential therapeutic target for metastasis. Cancers (Basel). 2024;16(1):234. doi: 10.3390/cancers16010234. DOI: https://doi.org/10.3390/cancers16010234
Jiao F, Hu H, Han T, Yuan C, Wang L, Jin Z, et al. Long noncoding RNA MALAT-1 enhances stem cell-like phenotypes in pancreatic cancer cells. Int J Mol Sci. 2015;16(4):6677–6693. doi: 10.3390/ijms16046677. DOI: https://doi.org/10.3390/ijms16046677
van den Boogaard WMC, Komninos DSJ, Vermeij WP. Chemotherapy side-effects: Not all DNA damage is equal. Cancers (Basel). 2022;14(3):627. doi: 10.3390/cancers14030627. DOI: https://doi.org/10.3390/cancers14030627
Moon J, Kitty I, Renata K, Qin S, Zhao F, Kim W. DNA damage and its role in cancer therapeutics. Int J Mol Sci. 2023;24(5):4741. doi: 10.3390/ijms24054741. DOI: https://doi.org/10.3390/ijms24054741
Zhou J, Kang Y, Chen L, Wang H, Liu J, Zeng S, et al. The drug-resistance mechanisms of five platinum-based antitumor agents. Front Pharmacol. 2020;11. doi: 10.3389/fphar.2020.00343. DOI: https://doi.org/10.3389/fphar.2020.00343
Xie X, Huang N, Zhang Y, Wei X, Gao M, Li M, et al. MiR-192-5p reverses cisplatin resistance by targeting ERCC3 and ERCC4 in SGC7901/DDP cells. J Cancer. 2019;10(4):1039–1051. doi: 10.7150/jca.25814. DOI: https://doi.org/10.7150/jca.25814
Sun C, Li N, Yang Z, Zhou B, He Y, Weng D, et al. miR-9 regulation of BRCA1 and ovarian cancer sensitivity to cisplatin and PARP inhibition. JNCI: J Natl Cancer Instit. 2013;105(22):1750–1758. doi: 10.1093/jnci/djt302. DOI: https://doi.org/10.1093/jnci/djt302
Chung YM, Park SH, Tsai WB, Wang SY, Ikeda MA, Berek JS, et al. FOXO3 signalling links ATM to the p53 apoptotic pathway following DNA damage. Nat Commun. 2012;3(1). doi: 10.1038/ncomms2008. DOI: https://doi.org/10.1038/ncomms2008
Kamalabadi-Farahani M, Atashi A, Eslami MM. Downregulation of circ-Foxo3 in breast cancer stem-like cells. BMC Res Notes. 2023;16(1). doi: 10.1186/s13104-023-06405-z. DOI: https://doi.org/10.1186/s13104-023-06405-z
Long F, Li X, Pan J, Ye H, Di C, Huang Y, et al. The role of lncRNA NEAT1 in human cancer chemoresistance. Cancer Cell Int. 2024;24(1). doi: 10.1186/s12935-024-03426-x. DOI: https://doi.org/10.1186/s12935-024-03426-x
Xu W, Wu Y, Zhang G. NEAT1 promotes the progression of prostate cancer by targeting the miR-582-5p/EZH2 regulatory axis. Cytotechnology. 2024;76(2):231–246. doi: 10.1007/s10616-023-00612-z. DOI: https://doi.org/10.1007/s10616-023-00612-z
Zhu M, Yang L, Wang X. NEAT1 Knockdown suppresses the cisplatin resistance in ovarian cancer by regulating miR-770-5p/PARP1 axis. Cancer Manag Res. 2020;12:7277–7289. doi: 10.2147/cmar.s257311. DOI: https://doi.org/10.2147/CMAR.S257311
Wu YC, Ku MH, Huang WL, Dias L, Chen CW. NEAT1 in ovarian xancer: A key regulator of tumor progression, follicular fluid dynamics, and therapeutic resistance. Anticancer Res. 2025;45(3):825–842. doi: 10.21873/anticanres.17472. DOI: https://doi.org/10.21873/anticanres.17472
Furuta E, Okuda H, Kobayashi A, Watabe K. Metabolic genes in cancer: Their roles in tumor progression and clinical implications. Biochimica et Biophysica Acta - Rev Cancer. 2010;1805(2):141–152. doi: 10.1016/j.bbcan.2010.01.005. DOI: https://doi.org/10.1016/j.bbcan.2010.01.005
Jang M, Kim SS, Lee J. Cancer cell metabolism: implications for therapeutic targets. Exp Mol Med. 2013;45(10):e45–e45. doi: 10.1038/emm.2013.85. DOI: https://doi.org/10.1038/emm.2013.85
Zhao M, Ma J, Li M, Zhang Y, Jiang B, Zhao X, et al. Cytochrome P450 enzymes and drug metabolism in humans. Int J Mol Sci. 2021;22(23):12808. doi: 10.3390/ijms222312808. DOI: https://doi.org/10.3390/ijms222312808
Kural C, Kaya Kocdogan A, Şimşek GG, Oğuztüzün S, Kaygın P, Yılmaz I, et al. Glutathione S-transferases and cytochrome P450 enzyme expression in patients with intracranial tumors: Preliminary report of 55 patients. Med Principles Pract. 2018;28(1):56–62. doi: 10.1159/000494496. DOI: https://doi.org/10.1159/000494496
Mu W, Hu C, Zhang H, Qu Z, Cen J, Qiu Z, et al. miR-27b synergizes with anticancer drugs via p53 activation and CYP1B1 suppression. Cell Res. 2015;25(4):477–495. doi: 10.1038/cr.2015.23. DOI: https://doi.org/10.1038/cr.2015.23
Pan YZ, Gao W, Yu AM. MicroRNAs regulate CYP3A4 expression via direct and indirect targeting. Drug Metab Dispos. 2009;37(10):2112–2117. doi: 10.1124/dmd.109.027680. DOI: https://doi.org/10.1124/dmd.109.027680
Kim I, Han N, Burckart GJ, Oh JM. Epigenetic changes in gene expression for drug‐metabolizing enzymes and transporters. Pharmacotherapy. 2013;34(2):140–150. doi: 10.1002/phar.1362. DOI: https://doi.org/10.1002/phar.1362
Klyushova LS, Perepechaeva ML, Grishanova AY. The role of CYP3A in health and disease. Biomedicines. 2022;10(11):2686. doi: 10.3390/biomedicines10112686. DOI: https://doi.org/10.3390/biomedicines10112686
Panda AC, Grammatikakis I, Munk R, Gorospe M, Abdelmohsen K. Emerging roles and context of circular RNAs. WIREs RNA. 2016;8(2). doi: 10.1002/wrna.1386. DOI: https://doi.org/10.1002/wrna.1386
Cai ZR, Hu Y, Liao K, Li H, Chen DL, Ju HQ. Circular RNAs: Emerging regulators of glucose metabolism in cancer. Cancer Lett. 2023;552:215978. doi: 10.1016/j.canlet.2022.215978. DOI: https://doi.org/10.1016/j.canlet.2022.215978
Huang Y, He T, Zheng J, Chen J, Yang Z. Circular RNAs in metabolic health: bridging the gap between molecular biology and therapy. Cell Death Dis. 2026;17(1). doi: 10.1038/s41419-026-08450-5. DOI: https://doi.org/10.1038/s41419-026-08450-5
Collins JM, Wang D. Regulation of CYP3A4 and CYP3A5 by a lncRNA: a potential underlying mechanism explaining the association between CYP3A4*1G and CYP3A metabolism. Pharmacogenet Genomics. 2021;32(1):16–23. doi: 10.1097/fpc.0000000000000447. DOI: https://doi.org/10.1097/FPC.0000000000000447
Wu H, Liu B, Chen Z, Li G, Zhang Z. MSC-induced lncRNA HCP5 drove fatty acid oxidation through miR-3619-5p/AMPK/PGC1α/CEBPB axis to promote stemness and chemo-resistance of gastric cancer. Cell Death Dis. 2020;11(4). doi: 10.1038/s41419-020-2426-z. DOI: https://doi.org/10.1038/s41419-020-2426-z
Meng X, Bai X, Ke A, Li K, Lei Y, Ding S, et al. Long non-coding RNAs in drug resistance of gastric cancer: Complex mechanisms and potential clinical applications. Biomolecules. 2024;14(6):608. doi: 10.3390/biom14060608. DOI: https://doi.org/10.3390/biom14060608
Havasi A, Cainap SS, Havasi AT, Cainap C. Ovarian cancer—insights into platinum resistance and overcoming it. Medicina (B Aires). 2023;59(3):544. doi: 10.3390/medicina59030544. DOI: https://doi.org/10.3390/medicina59030544
Al-Janabi I. The role of autophagy in the progression and treatment of tumors. Al-Rafidain J Med Sci. 2021;1:62–71. doi: 10.54133/ajms.v1i.37. DOI: https://doi.org/10.54133/ajms.v1i.37
Klionsky DJ, Codogno P, Cuervo AM, Deretic V, Elazar Z, Fueyo-Margareto J, et al. A comprehensive glossary of autophagy-related molecules and processes. Autophagy. 2010;6(4):438–448. doi: 10.4161/auto.6.4.12244. DOI: https://doi.org/10.4161/auto.6.4.12244
Chen W, Li Z, Liu H, Jiang S, Wang G, Sun L, et al. MicroRNA-30a targets BECLIN-1 to inactivate autophagy and sensitizes gastrointestinal stromal tumor cells to imatinib. Cell Death Dis. 2020;11(3). doi: 10.1038/s41419-020-2390-7. DOI: https://doi.org/10.1038/s41419-020-2390-7
Yang Y, Guo JX, Shao ZQ. miR-21 targets and inhibits tumor suppressor gene PTEN to promote prostate cancer cell proliferation and invasion: An experimental study. Asian Pac J Trop Med. 2017;10(1):87–91. doi: 10.1016/j.apjtm.2016.09.011. DOI: https://doi.org/10.1016/j.apjtm.2016.09.011
Chen C, Demirkhanyan L, Gondi CS. The Multifaceted role of miR-21 in pancreatic cancers. Cells. 2024;13(11):948. doi: 10.3390/cells13110948. DOI: https://doi.org/10.3390/cells13110948
Yao W, Guo P, Mu Q, Wang Y. Exosome-derived circ-PVT1 contributes to cisplatin resistance by regulating autophagy, invasion, and apoptosis via miR-30a-5p/YAP1 axis in gastric cancer cells. Cancer Biother Radiopharm. 2021;36(4):347–359. doi: 10.1089/cbr.2020.3578. DOI: https://doi.org/10.1089/cbr.2020.3578
Fu Z, Luo W, Wang J, Peng T, Sun G, Shi J, et al. Malat1 activates autophagy and promotes cell proliferation by sponging miR-101 and upregulating STMN1, RAB5A and ATG4D expression in glioma. Biochem Biophys Res Commun. 2017;492(3):480–486. doi: 10.1016/j.bbrc.2017.08.070. DOI: https://doi.org/10.1016/j.bbrc.2017.08.070
Nguyen LNT, Pyburn JS, Nguyen NL, Schank MB, Zhao J, Wang L, et al. Epigenetic regulation by lncRNA GAS5/miRNA/mRNA network in human diseases. Int J Mol Sci. 2025;26(3):1377. doi: 10.3390/ijms26031377. DOI: https://doi.org/10.3390/ijms26031377
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2026 Al-Rafidain Journal of Medical Sciences ( ISSN 2789-3219 )

This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
Published by Al-Rafidain University College. This is an open access journal issued under the CC BY-NC-SA 4.0 license (https://creativecommons.org/licenses/by-nc-sa/4.0/).



