Functional significance of miR-218 in lung cancer

Abstract

Lung cancer remains one of the most prevalent and lethal malignancies worldwide, characterized by a poor prognosis and high mortality rates. Although therapeutic strategies targeting oncogenic signaling cascades, such as receptor tyrosine kinases, have shown promising outcomes by regulating cellular functions such as survival and proliferation, their long-term effectiveness is often limited by mechanisms, including tumor resistance, drug toxicity, and adverse events. These challenges underscore the urgent need to identify new molecular targets and develop alternative therapeutic approaches. One promising avenue lies in the exploration of microRNAs (miRs) and their significance in cancer biology. Among them, miR-218 has drawn significant attention for its tumor-suppressive properties. Multiple experimental studies have emphasized the role of miR-218 as a key regulator of cell signaling pathways critical to cancer progression, including proliferation, invasion, metastasis, and apoptosis. Notably, miR-218 has been investigated as both a diagnostic biomarker and a therapeutic target. Importantly, clinical evidence further supports its relevance, showing an inverse correlation between miR-218 expression levels and tumor aggressiveness, reinforcing its translational significance. This review logically consolidates the functional significance, mechanistic insights, and experimental and clinical findings that emphasize the pivotal role of miR-218 in regulating molecular pathways involved in lung cancer growth.

Keywords

Lung cancer / miR-218 / cell signaling pathways / tumor suppressors / metastasis / chemotherapy sensitivity / radiation therapy

References

[1] Bray F,Sung H.Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries.CA Cancer J Clin2024;74:229-63

[2] Siegel RL,Giaquinto AN,Jemal A.Cancer statistics, 2025.CA Cancer J Clin2025;75:10-45 PMCID:PMC11745215

[3] Siegel RL,Jemal A.Cancer statistics, 2024.CA Cancer J Clin2024;74:12-49

[4] Inamura K.Lung cancer: understanding its molecular pathology and the 2015 WHO classification.Front Oncol2017;7:193 PMCID:PMC5581350

[5] Zheng M.Classification and pathology of lung cancer.Surg Oncol Clin N Am2016;25:447-68

[6] Travis WD, Brambilla E, Nicholson AG, et al.; WHO Panel. The 2015 World Health Organization Classification of lung tumors: impact of genetic, clinical and radiologic advances since the 2004 classification.J Thorac Oncol2015;10:1243-60

[7] Yendamuri S,Pine M.Outcomes of sarcomatoid carcinoma of the lung: a surveillance, epidemiology, and end results database analysis.Surgery2012;152:397-402

[8] Hendriks LEL,Faivre-Finn C.Non-small-cell lung cancer.Nat Rev Dis Primers2024;10:71

[9] Chevallier M,Addeo A.Oncogenic driver mutations in non-small cell lung cancer: past, present and future.World J Clin Oncol2021;12:217-37 PMCID:PMC8085514

[10] Xie S,Qi Y,Zhu X.The metastasizing mechanisms of lung cancer: Recent advances and therapeutic challenges.Biomed Pharmacother2021;138:111450

[11] Li W,Huang Q.Advancement of regulating cellular signaling pathways in NSCLC target therapy via nanodrug.Front Chem2023;11:1251986 PMCID:PMC10512551

[12] Alamri S,Zorgi S.Disease prognosis and therapeutic strategies in patients with advanced non-small cell lung cancer (NSCLC): a 6-year epidemiological study between 2015-2021.Transl Cancer Res2024;13:762-70

[13] Gildea TR,Hogarth DK,Quinn CC.A retrospective analysis of delays in the diagnosis of lung cancer and associated costs.Clinicoecon Outcomes Res2017;9:261-9 PMCID:PMC5440037

[14] Kocher F,Seeber A.Longitudinal analysis of 2293 NSCLC patients: a comprehensive study from the TYROL registry.Lung Cancer2015;87:193-200

[15] Samson JS.Prospects of microRNAs as therapeutic biomarkers in non-small cell lung cancer.Med Oncol2023;40:345

[16] Shimamura SS,Asao T.Survival past five years with advanced, EGFR-mutated or ALK-rearranged non-small cell lung cancer-is there a “tail plateau” in the survival curve of these patients?.BMC Cancer2022;22:323

[17] Garon EB,Rizvi NA.Five-year overall survival for patients with advanced non-small-cell lung cancer treated with pembrolizumab: results from the phase I KEYNOTE-001 study.J Clin Oncol2019;37:2518-27

[18] Lu T,Huang Y.Trends in the incidence, treatment, and survival of patients with lung cancer in the last four decades.Cancer Manag Res2019;11:943-53

[19] Kneuertz PJ,Altorki NK.Sublobar resection vs lobectomy for stage ia non-small cell lung carcinoma-takeaways from modern randomized trials.Ann Thorac Surg2024;117:897-903

[20] Matsuda A,Kunitoh H.Quality of life with docetaxel plus cisplatin versus paclitaxel plus carboplatin in patients with completely resected non-small cell lung cancer: quality of life analysis of TORG 0503.Qual Life Res2023;32:2629-37

[21] Schneider BJ,Kennedy EB.Stereotactic body radiotherapy for early-stage non-small-cell lung cancer: American Society of clinical oncology endorsement of the American Society for radiation oncology evidence-based guideline.J Clin Oncol2018;36:710-9

[22] Brozos-Vázquez EM,García-González J.Immunotherapy in nonsmall-cell lung cancer: current status and future prospects for liquid biopsy.Cancer Immunol Immunother2021;70:1177-88 PMCID:PMC10991125

[23] Lu Y,Zhang H.Nano-immunotherapy for lung cancer.Nano TransMed2023;2:e9130018Available from https://www.sciencedirect.com/science/article/pii/S2790676023000365 [accessed 5 February 2026].

[24] Hsu PC,Yang CT.Epidermal growth factor receptor (EGFR) pathway, yes-associated protein (YAP) and the regulation of programmed death-ligand 1 (PD-L1) in non-small cell lung cancer (NSCLC).Int J Mol Sci2019;20:3821 PMCID:PMC6695603

[25] Tran TO,Le NQK.Hyper-methylation of ABCG1 as an epigenetics biomarker in non-small cell lung cancer.Funct Integr Genomics2023;23:256

[26] Wu Y,Zhou Q.Expert consensus on treatment for stage III non‐small cell lung cancer.Medicine Advances2023;1:3-13

[27] Saw SPL,Chua KLM,Tan DSW.Revisiting neoadjuvant therapy in non-small-cell lung cancer.Lancet Oncol2021;22:e501-16

[28] Thyagarajan A,Sahu RP.Are metformin-based combination approaches beneficial for non-small cell lung cancer: evidence from experimental and clinical studies.Mil Med Res2025;12:61 PMCID:PMC12455790

[29] Pesch B,Gustavsson P.Cigarette smoking and lung cancer--relative risk estimates for the major histological types from a pooled analysis of case-control studies.Int J Cancer2012;131:1210-9

[30] Le Calvez F,Hunt JD.TP53 and KRAS mutation load and types in lung cancers in relation to tobacco smoke: distinct patterns in never, former, and current smokers.Cancer Res2005;65:5076-83

[31] Wynder EL.Tobacco smoking as a possible etiologic factor in bronchiogenic carcinoma: a study of six hundred and eighty-four proved cases.J Am Med Assoc1950;143:329-36

[32] Krewski D,Zielinski JM.Residential radon and risk of lung cancer: a combined analysis of 7 North American case-control studies.Epidemiology2005;16:137-45

[33] Boffetta P,Boniol M.An estimate of cancers attributable to occupational exposures in France.J Occup Environ Med2010;52:399-406

[34] Lissowska J,Fletcher T.Lung cancer and indoor pollution from heating and cooking with solid fuels: the IARC international multicentre case-control study in Eastern/Central Europe and the United Kingdom.Am J Epidemiol2005;162:326-33

[35] Ling B,Huang Y.Identification of prognostic markers of lung cancer through bioinformatics analysis and in vitro experiments.Int J Oncol2020;56:193-205 PMCID:PMC6910184

[36] Thyagarajan A,Sahu RP.MicroRNA heterogeneity in melanoma progression.Semin Cancer Biol2019;59:208-20 PMCID:PMC6885122

[37] Hamdy NM,El-Sisi MG.Advancements in current one-size-fits-all therapies compared to future treatment innovations for better improved chemotherapeutic outcomes: a step-toward personalized medicine.Curr Med Res Opin2024;40:1943-61

[38] Lu TX.MicroRNA.J Allergy Clin Immunol2018;141:1202-7 PMCID:PMC5889965

[39] Chauhan SJ,Sahu RP.Effects of miRNA-149-5p and platelet-activating factor-receptor signaling on the growth and targeted therapy response on lung cancer cells.Int J Mol Sci2022;23:6772 PMCID:PMC9223644

[40] Bernstein E,Hammond SM.Role for a bidentate ribonuclease in the initiation step of RNA interference.Nature2001;409:363-6

[41] Walayat A,Xiao D.Therapeutic implication of miRNA in human disease. In: Sharad S, Kapur S, editors. Antisense therapy. IntechOpen; 2018.

[42] O'Brien J,Zayed Y.Overview of MicroRNA biogenesis, mechanisms of actions, and circulation.Front Endocrinol2018;9:402 PMCID:PMC6085463

[43] Wang F,Zhou Y.Down-regulation of the cyclin E1 oncogene expression by microRNA-16-1 induces cell cycle arrest in human cancer cells.BMB Rep2009;42:725-30 PMCID:PMC6604625

[44] Sun F,Liu Q.Downregulation of CCND1 and CDK6 by miR-34a induces cell cycle arrest.FEBS Lett2008;582:1564-8

[45] Luo J,Wang H,Zhou J.MicroRNA-126 affects ovarian cancer cell differentiation and invasion by modulating expression of vascular endothelial growth factor.Oncol Lett2018;15:5803-8 PMCID:PMC5840569

[46] Lang Y,Liu B,Chen L.microRNA-651-5p affects the proliferation, migration, and invasion of lung cancer cells by regulating calmodulin 2 expression.Clin Respir J2023;17:754-63

[47] Qin W,Zhao B.miR-24 regulates apoptosis by targeting the open reading frame (ORF) region of FAF1 in cancer cells.PLoS One2010;5:e9429 PMCID:PMC2828487

[48] Cui F,Xiao K.The microRNA hsa-let-7g promotes proliferation and inhibits apoptosis in lung cancer by targeting HOXB1.Yonsei Med J2020;61:210-7 PMCID:PMC7044691

[49] Tüfekci KU,Genç Ş.The Role of MicroRNAs in biological processes. In: Yousef M, Allmer J, editors. miRNomics: microRNA biology and computational analysis. Totowa: Humana Press; 2014. pp. 15-31.

[50] You J,Fang N.MiR-132 suppresses the migration and invasion of lung cancer cells via targeting the EMT regulator ZEB2.PLoS One2014;9:e91827 PMCID:PMC3953608

[51] Li J,Wang Y,Yu W.MicroRNA-148a suppresses epithelial-to-mesenchymal transition by targeting ROCK1 in non-small cell lung cancer cells.Mol Cell Biochem2013;380:277-82

[52] Thyagarajan A,Sahu RP.MicroRNA-directed cancer therapies: implications in melanoma intervention.J Pharmacol Exp Ther2018;364:1-12 PMCID:PMC5733457

[53] Cortez MA,Zhang X.Therapeutic delivery of miR-200c enhances radiosensitivity in lung cancer.Mol Ther2014;22:1494-503 PMCID:PMC4435581

[54] Zhao Z,Yao Q.miR-15b regulates cisplatin resistance and metastasis by targeting PEBP4 in human lung adenocarcinoma cells.Cancer Gene Ther2015;22:108-14

[55] Yu S,Chen T,Xu X.MicroRNA-106b-5p regulates cisplatin chemosensitivity by targeting polycystic kidney disease-2 in non-small-cell lung cancer.Anticancer Drugs2017;28:852-60

[56] Yang Y,Hu Q.MicroRNA-218 functions as a tumor suppressor in lung cancer by targeting IL-6/STAT3 and negatively correlates with poor prognosis.Mol Cancer2017;16:141 PMCID:PMC5567631

[57] Tatarano S,Kawakami K.miR-218 on the genomic loss region of chromosome 4p15.31 functions as a tumor suppressor in bladder cancer.Int J Oncol2011;39:13-21

[58] Davidson MR,Yang IA.MicroRNA-218 is deleted and downregulated in lung squamous cell carcinoma.PLoS One2010;5:e12560 PMCID:PMC2933228

[59] Rodriguez A,Ashurst JL.Identification of mammalian microRNA host genes and transcription units.Genome Res2004;14:1902-10 PMCID:PMC524413

[60] Charostad J,Azaran A.MiRNA-218 is frequently downregulated in malignant breast tumors: a footprint of epstein-barr virus infection.Iran J Pathol2021;16:376-85

[61] Shi J,Wang T.miR-218 is downregulated and directly targets SH3GL1 in childhood medulloblastoma.Mol Med Rep2013;8:1111-7

[62] Guan B,Zhang L.MicroRNA-218 inhibits the migration, epithelial-mesenchymal transition and cancer stem cell properties of prostate cancer cells.Oncol Lett2018;16:1821-6

[63] Hu L,Long H.Integrative microRNA and gene profiling data analysis reveals novel biomarkers and mechanisms for lung cancer.Oncotarget2016;7:8441-54 PMCID:PMC4890978

[64] Zhao L,Wang Y.Long noncoding RNA CCAT1 enhances human nonsmall cell lung cancer growth through downregulation of microRNA218.Oncol Rep2020;43:1045-52 PMCID:PMC7057767

[65] Jin X,Zhang Z.lncRNA CCAT1 acts as a MicroRNA-218 sponge to increase gefitinib resistance in NSCLC by targeting HOXA1.Mol Ther Nucleic Acids2020;19:1266-75 PMCID:PMC7029377

[66] Wischmann FJ,Frankenberg M.Tumor suppressor miR-218 directly targets epidermal growth factor receptor (EGFR) expression in triple-negative breast cancer, sensitizing cells to irradiation.J Cancer Res Clin Oncol2023;149:8455-65 PMCID:PMC10374822

[67] Lun W,Deng Q.MiR-218 regulates epithelial-mesenchymal transition and angiogenesis in colorectal cancer via targeting CTGF.Cancer Cell Int2018;18:83 PMCID:PMC5994014

[68] Li L,Ren Q.MiR-218-5p suppresses the progression of retinoblastoma through targeting NACC1 and inhibiting the AKT/mTOR signaling pathway.Cancer Manag Res2020;12:6959-67

[69] Cruz-De la Rosa MI,Alarcón-Millán J.miR-218-5p/RUNX2 axis positively regulates proliferation and is associated with poor prognosis in cervical cancer.Int J Mol Sci2022;23:6993 PMCID:PMC9267020

[70] Han M,Wang Y.miR-218 overexpression suppresses tumorigenesis of papillary thyroid cancer via inactivation of PTEN/PI3K/AKT pathway by targeting Runx2.Onco Targets Ther2018;11:6305-16

[71] Guo P,Liu H,Yang N.Effects of miR-218-1-3p and miR-149 on proliferation and apoptosis of non-small cell lung cancer cells.Oncol Lett2020;20:96

[72] Chen Y,Xue ZZ.Effects and mechanism of microRNA218 against lung cancer.Mol Med Rep2021;23:1-1 PMCID:PMC7673340

[73] Zhu K,Wang W.Tumor-suppressive miR-218-5p inhibits cancer cell proliferation and migration via EGFR in non-small cell lung cancer.Oncotarget2016;7:28075-85 PMCID:PMC5053710

[74] Wu DW,Wang J,Lee H.Paxillin predicts survival and relapse in non-small cell lung cancer by microRNA-218 targeting.Cancer Res2010;70:10392-401

[75] Zarogoulidis P,Kioseoglou E,Anestakis D.MiR-205 and miR-218 expression is associated with carboplatin chemoresistance and regulation of apoptosis via Mcl-1 and Survivin in lung cancer cells.Cell Signal2015;27:1576-88

[76] Chiu KL,Kuok QY.ADAM9 enhances CDCP1 protein expression by suppressing miR-218 for lung tumor metastasis.Sci Rep2015;5:16426

[77] Zeng XJ,Luo M,and Yu H.Inhibition of pulmonary carcinoma proliferation or metastasis of miR-218 via down-regulating CDCP1 expression.Eur Rev Med Pharmacol Sci2017;21:1502-8Available from https://www.europeanreview.org/article/12517 [accessed 5 February 2026].

[78] Lai X,Zhu C.Regulation of RPTPα-c-Src signalling pathway by miR-218.FEBS J2015;282:2722-34

[79] Li YJ,Xia H.miR-218 suppresses epithelial-to-mesenchymal transition by targeting Robo1 and Ecop in lung adenocarcinoma cells.Future Oncol2017;13:2571-82

[80] Wang Z,Wang K.Targeting TRIM9 by miR-218-5p restricts cell proliferation and epithelial-mesenchymal transition in non-small cell lung cancer.Ann Clin Lab Sci2023;53:106-15Available from https://www.annclinlabsci.org/content/53/1/106.short [accessed 5 February 2026].

[81] Zhang C,Hu C,Zhang J.MiRNA-218, a new regulator of HMGB1, suppresses cell migration and invasion in non-small cell lung cancer.Acta Biochim Biophys Sin2013;45:1055-61

[82] Sher YP,Chuang LL.ADAM9 up-regulates N-cadherin via miR-218 suppression in lung adenocarcinoma cells.PLoS One2014;9:e94065 PMCID:PMC3976390

[83] Shi ZM,Shen H.Downregulation of miR-218 contributes to epithelial-mesenchymal transition and tumor metastasis in lung cancer by targeting Slug/ZEB2 signaling.Oncogene2017;36:2577-88

[84] Chen P,Li Y.MiR-218 inhibits migration and invasion of lung cancer cell by regulating Robo1 expression.Chin J Lung Cancer2017;20:452-8

[85] Zhang Z,Wang Y.Heparan sulfate D-glucosamine 3-O-sulfotransferase 3B1 is a novel regulator of transforming growth factor-beta-mediated epithelial-to-mesenchymal transition and regulated by miR-218 in nonsmall cell lung cancer.J Cancer Res Ther2018;14:24-9

[86] Song L,Zhao Y.miR-218 suppressed the growth of lung carcinoma by reducing MEF2D expression.Tumour Biol2016;37:2891-900

[87] Chen Y,Han F.Use of recombinant microRNAs as antimetabolites to inhibit human non-small cell lung cancer.Acta Pharm Sin B2023;13:4273-90 PMCID:PMC10547963

[88] Chen G,Wang K.MicroRNA-218-5p affects lung adenocarcinoma progression through targeting endoplasmic reticulum oxidoreductase 1 alpha.Bioengineered2022;13:10061-70 PMCID:PMC9161986

[89] Tian W,Song Y.miR-218 inhibits glucose metabolism in non-small cell lung cancer via the NF-κB signaling pathway.Exp Ther Med2021;21:106

[90] Xie J,Li D,Zhang X.MicroRNA-218 regulates cisplatin (DPP) chemosensitivity in non-small cell lung cancer by targeting RUNX2.Tumour Biol2016;37:1197-204

[91] Chen X,Jiang L.miRNA-218-5p increases cell sensitivity by inhibiting PRKDC activity in radiation-resistant lung carcinoma cells.Thorac Cancer2021;12:1549-57

[92] Wang X,Shi H.TRIM9 is up-regulated in human lung cancer and involved in cell proliferation and apoptosis.Int J Clin Exp Med2016;9:10461-9Available from https://e-century.us/files/ijcem/9/6/ijcem0020617.pdf [accessed 5 February 2026].

[93] Yang F,Yu Y.TRIM9 overexpression promotes uterine leiomyoma cell proliferation and inhibits cell apoptosis via NF-κB signaling pathway.Life Sci2020;257:118101

[94] Zhang YL,Wang KF.The prevalence of EGFR mutation in patients with non-small cell lung cancer: a systematic review and meta-analysis.Oncotarget2016;7:78985-93

[95] Kalluri R.Epithelial-mesenchymal transition and its implications for fibrosis.J Clin Invest2003;112:1776-84 PMCID:PMC297008

[96] Liu PL,Hwang JJ.High-mobility group box 1-mediated matrix metalloproteinase-9 expression in non-small cell lung cancer contributes to tumor cell invasiveness.Am J Respir Cell Mol Biol2010;43:530-8

[97] Tsoukalas N,Tolia M.Epithelial-mesenchymal transition in non small-cell lung cancer.Anticancer Res2017;37:1773-8

[98] Schmid BC,Fabjani G,Leodolter S.The neuronal guidance cue Slit2 induces targeted migration and may play a role in brain metastasis of breast cancer cells.Breast Cancer Res Treat2007;106:333-42

[99] Park S.ECop (EGFR-coamplified and overexpressed protein), a novel protein, regulates NF-κB transcriptional activity and associated apoptotic response in an IκBα-dependent manner.Oncogene2005;24:2495-502

[100] Wang Y,Yu Y,Zheng H.Knockdown of SNHG12 suppresses tumor metastasis and epithelial-mesenchymal transition via the Slug/ZEB2 signaling pathway by targeting miR-218 in NSCLC.Oncol Lett2019;17:2356-64

[101] Wang P,Ma H.LncRNA SNHG12 contributes to multidrug resistance through activating the MAPK/Slug pathway by sponging miR-181a in non-small cell lung cancer.Oncotarget2017;8:84086-101 PMCID:PMC5663579

[102] Su L,Yang Z.MEF2D transduces microenvironment stimuli to ZEB1 to promote epithelial-mesenchymal transition and metastasis in colorectal cancer.Cancer Res2016;76:5054-67

[103] Liu H,Badu-Nkansah K,White FM.CUB-domain-containing protein 1 (CDCP1) activates Src to promote melanoma metastasis.Proc Natl Acad Sci U S A2011;108:1379-84 PMCID:PMC3029734

[104] Hooper JD,Aimes RT.Subtractive immunization using highly metastatic human tumor cells identifies SIMA135/CDCP1, a 135 kDa cell surface phosphorylated glycoprotein antigen.Oncogene2003;22:1783-94

[105] Ikeda J,Inoue M.Expression of CUB domain containing protein (CDCP1) is correlated with prognosis and survival of patients with adenocarcinoma of lung.Cancer Sci2009;100:429-33 PMCID:PMC11158370

[106] Liu TC,Wu WJ.Association between survivin genetic polymorphisms and epidermal growth factor receptor mutation in non-small-cell lung cancer.Int J Med Sci2016;13:929-35 PMCID:PMC5165686

[107] Jacobs JJ,Marino S,van Lohuizen M.The oncogene and polycomb-group gene bmi-1 regulates cell proliferation and senescence through the ink4a locus.Nature1999;397:164-8

[108] Sirhan Z,Thyagarajan A.Therapeutic implications of PTEN in non-small cell lung cancer.Pharmaceutics2023;15:2090 PMCID:PMC10458395

[109] Paone A,Fiascarelli A.SHMT1 knockdown induces apoptosis in lung cancer cells by causing uracil misincorporation.Cell Death Dis2014;5:e1525 PMCID:PMC4260740

[110] O’Byrne KJ,Giatromanolaki A.Vascular endothelial growth factor, platelet-derived endothelial cell growth factor and angiogenesis in non-small-cell lung cancer.Br J Cancer2000;82:1427-32 PMCID:PMC2363365

[111] Zhang L,Zhou L.Heparan sulfate D-glucosaminyl 3-O-sulfotransferase-3B1 (HS3ST3B1) promotes angiogenesis and proliferation by induction of VEGF in acute myeloid leukemia cells.J Cell Biochem2015;116:1101-12

[112] Huang B,Li X.The role of IL-6/JAK2/STAT3 signaling pathway in cancers.Front Oncol2022;12:1023177 PMCID:PMC9800921

[113] Gu Z,Li C.Increased PTPRA expression leads to poor prognosis through c-Src activation and G1 phase progression in squamous cell lung cancer.Int J Oncol2017;51:489-97 PMCID:PMC5505127

[114] Warburg O,Negelein E.The metabolism of tumors in the body.J Gen Physiol1927;8:519-30 PMCID:PMC2140820

[115] Lin TC.RUNX2 and cancer.Int J Mol Sci2023;24:7001 PMCID:PMC10139076

[116] Zhang Y,He RQ.Upregulation of HOXA1 promotes tumorigenesis and development of nonsmall cell lung cancer: a comprehensive investigation based on reverse transcription-quantitative polymerase chain reaction and bioinformatics analysis.Int J Oncol2018;53:73-86 PMCID:PMC5958640

[117] Simone CB 2nd,Chen AB.ASTRO radiation therapy summary of the ASCO guideline on management of stage III non-small cell lung cancer.Pract Radiat Oncol2023;13:195-202

[118] Chen Y,Xiong J.Role of PRKDC in cancer initiation, progression, and treatment.Cancer Cell Int2021;21:563 PMCID:PMC8547028

[119] Yang Q,Hu Y.MiR-218-5p suppresses the killing effect of natural killer cell to lung adenocarcinoma by targeting SHMT1.Yonsei Med J2019;60:500-8 PMCID:PMC6536398

[120] Morton JJ,Refaeli Y.Humanized mouse xenograft models: narrowing the tumor-microenvironment gap.Cancer Res2016;76:6153-8 PMCID:PMC5093075

[121] Dong H,Ding L,Ju H.MicroRNA: function, detection, and bioanalysis.Chem Rev2013;113:6207-33

[122] Qian W,Sheng Y.Tumor purity in preclinical mouse tumor models.Cancer Res Commun2022;2:353-65

[123] Carretta M,Schina A.Dissecting tumor microenvironment heterogeneity in syngeneic mouse models: insights on cancer-associated fibroblast phenotypes shaped by infiltrating T cells.Front Immunol2023;14:1320614 PMCID:PMC10800379

[124] Gu A,Li MY.Patient-derived xenograft model in cancer: establishment and applications.MedComm2025;6:e70059

[125] Ye G,Huang L.miRNA-218/FANCI is associated with metastasis and poor prognosis in lung adenocarcinoma: a bioinformatics analysis.Ann Transl Med2021;9:1298 PMCID:PMC8422123

[126] Khorshid O,Makar HAS,Elsayed AHH.Prognostic significance of circulating Mir-182-5p and Mir-218-5p as liquid biopsy biomarkers in advanced non-small cell lung cancer.Int J Environ Sci2025;11:1336-42

[127] Brillante S,Indrieri A.Advances in MicroRNA therapeutics: from preclinical to clinical studies.Hum Gene Ther2024;35:628-48

[128] Tian H,Liang Y.MicroRNA therapeutic delivery strategies: a review.J Drug Deliv Sci Technol2024;93:105430

[129] Momin MY,Kravitz M,Vikram A.The challenges and opportunities in the development of MicroRNA therapeutics: a multidisciplinary viewpoint.Cells2021;10:3097 PMCID:PMC8619171

[130] Wang J,Ge Q.Characterization of microRNA transcriptome in tumor, adjacent, and normal tissues of lung squamous cell carcinoma.J Thorac Cardiovasc Surg2015;149:1404-14.e4

[131] Kumamoto T,Mataki H.Regulation of TPD52 by antitumor microRNA-218 suppresses cancer cell migration and invasion in lung squamous cell carcinoma.Int J Oncol2016;49:1870-80 PMCID:PMC5063422

[132] Zeng F,Wang S.Linc00173 promotes chemoresistance and progression of small cell lung cancer by sponging miR-218 to regulate Etk expression.Oncogene2020;39:293-307