The expression and biological functions of miR-125b-5p in oral squamous cell carcinoma

doi:10.19438/j.cjoms.2025.06.001

Abstract

Abstract: PURPOSE: To explore the expression and biological function of miR-125b-5p in oral squamous cell carcinoma. METHODS: The expression of miR-125b-5p in OSCC and its correlation with prognosis was analyzed by TCGA database. The expression of miR-125b-5p in OSCC tissue samples and cell lines was analyzed by miRNA sequencing and RT-qPCR. The effect of miR-125b-5p overexpression on OSCC cell proliferation was detected by CCK-8 and colony formation assays. The effect of miR-125b-5p overexpression on OSCC cell migration was investigated by wound healing assay. The effect of miR-125b-5p overexpression on apoptosis of OSCC cells was evaluated by flow cytometry. Target genes of miR-125b-5p were identified through TargetScan, miRDB and miRTarBase databases. These predictions were validated through Western blotting, and the biological functions of the target genes were explored using KEGG and GO enrichment analyses. RESULTS: The expression of miR-125b-5p was significantly down-regulated in OSCC. Patients with lower expression of miR-125b-5p had significantly shorter overall survival(P=0.007) and disease-specific survival(P=0.022) compared to those with higher expression. Overexpression of miR-125b-5p significantly reduced the proliferative activity(P<0.001), colony formation ability (P<0.01) and migration capacity (P<0.001) of OSCC cells compared to the normal controls. Additionally, the apoptosis rate of miR-125b-5p overexpressing cells was significantly higher(P<0.001). Functional enrichment analysis suggested that the target genes of miR-125b-5p were involved in the regulation of tumor proliferation, apoptosis, migration and tumor immune microenvironment. CONCLUSIONS: The expression of miR-125b-5p is significantly down-regulated in OSCC. Overexpression of miR-125b-5p inhibits the proliferation and migration of OSCC cells and promotes cell apoptosis, may be a potential therapeutic target for OSCC treatment.

Key words: Oral squamous cell carcinoma, miR-125b-5p, Biological function, Apoptosis, Prognosis

CLC Number:

R739.8

Liu Jinghao, Guo Haiyan, Gan Guifang, Zhou Xinxia, Chen Fuxiang. The expression and biological functions of miR-125b-5p in oral squamous cell carcinoma[J]. China Journal of Oral and Maxillofacial Surgery, 2025, 23(6): 537-545.

References

[1] Bray F, Laversanne M, Sung H, et al.Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2024, 74(3): 229-263.
[2] Sung H, Ferlay J, Siegel RL, et al.Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2021, 71(3): 209-249.
[3] Han B, Zheng R, Zeng H, et al.Cancer incidence and mortality in China, 2022[J]. J Natl Cancer Cent, 2024, 4(1): 47-53.
[4] Chow LQM.Head and neck cancer[J]. N Engl J Med, 2020, 382(1): 60-72.
[5] Chen W, Zheng R, Baade PD, et al.Cancer statistics in China, 2015[J]. CA Cancer J Clin, 2016, 66(2): 115-132.
[6] Warnakulasuriya S.Global epidemiology of oral and oropharyngeal cancer[J]. Oral Oncol, 2009, 45(4-5): 309-316.
[7] Pfister DG, Spencer S, Brizel DM, et al.Head and neck cancers, version 2.2014. Clinical practice guidelines in oncology[J]. J Natl Compr Canc Netw, 2014, 12(10): 1454-1487.
[8] Siegel RL, Giaquinto AN, Jemal A.Cancer statistics, 2024[J]. CA Cancer J Clin, 2024, 74(1): 12-49.
[9] Lee YS, Dutta A.MicroRNAs in cancer[J]. Annu Rev Pathol, 2009, 4: 199-227.
[10] 秦晓丹,孙慧玲,潘蓓,等. miR-1229-3p 抑制结直肠癌疾病进展及作为潜在生物标志物的研究[J]. 诊断学理论与实践,2023, 22(5): 429-440.
Qin XD, Sun HL, Pan B, et al.miR-1229-3p inhibits the malignant progression of colorectal cancer and serves as a potential biomarker[J]. Journal of Diagnostics Concepts & Practice, 2023, 22(5): 429-440.
[11] Rupaimoole R, Slack FJ.MicroRNA therapeutics: towards a new era for the management of cancer and other diseases[J]. Nat Rev Drug Discov, 2017, 16(3): 203-222.
[12] Wen Z, Huang G, Lai Y, et al.Diagnostic panel of serum miR-125b-5p, miR-182-5p, and miR-200c-3p as non-invasive biomarkers for urothelial bladder cancer[J]. Clin Transl Oncol, 2022, 24(5): 909-918.
[13] Huo X, Wang K, Yao B, et al.Function and regulation of miR-186-5p, miR-125b-5p and miR-1260a in chordoma[J]. Bmc Cancer, 2023, 23(1): 1152.
[14] Towle R, Dickman CTD, MacLellan S A, et al. Identification of a serum-based microRNA signature that detects recurrent oral squamous cell carcinoma before it is clinically evident[J]. Brit J Cancer, 2023, 129(11): 1810-1817.
[15] 吕飞飞,李昆珊,胡燕,等. circVAPA 通过 miR-125b/HOXA7 轴逆转口腔癌细胞化疗耐药的机制研究[J]. 现代肿瘤医学, 2023, 31(8): 1398-1404.
Lyu FF, Li KS, Hu Y, et al.Mechanism of circVAPA in reversing chemoresistance of oral cancer cells through miR-125b/HOXA7 axis[J]. Journal of Modern Oncology, 2023, 31(8): 1398-1404.
[16] Mete O, Wenig BM.Update from the 5th Edition of the World Health Organization classification of head and neck tumors: overview of the 2022 WHO Classification of head and neck neuroendocrine neoplasms[J]. Head Neck Pathol, 2022, 16(1): 123-142.
[17] Jiang M, Yang Y, Niu L, et al.MiR-125b-5p modulates the function of regulatory T cells in tumor microenvironment by targeting TNFR2[J]. J Immunother Cancer, 2022, 10(11): e005241.
[18] Ferraresso M, Bailey S, Alonso-Crisostomo L, et al.Replenishing co-downregulated miR-100-5p and miR-125b-5p in malignant germ cell tumors causes growth inhibition through cell cycle disruption[J]. Mol Oncol, 2025, 19(4): 1203-1228.
[19] Chen YF, Wei YY, Yang CC, et al.miR-125b suppresses oral oncogenicity by targeting the anti-oxidative gene PRXL2A[J]. Redox Biol, 2019, 22: 101140.
[20] Yu Y, MohamedAl-Sharani H, Zhang B. EZH2-mediated SLC7A11 upregulation via miR-125b-5p represses ferroptosis of TSCC[J]. Oral Dis, 2023, 29(3): 880-891.
[21] Wu M, Gao X, Tang Y, et al.Cbl-b inhibited CD4+ T cell activation by regulating the expression of miR-99a/miR-125b[J]. Int Immunopharmacol, 2023, 115: 109677.
[22] Song L, Wang X, Qu X, et al.Transcription factor specificity protein 1 regulates inflammation and fibrin deposition in nasal polyps via the regulation of microRNA-125b and the Wnt/β-catenin signaling pathway[J]. Inflammation, 2022, 45(3): 1118-1132.
[23] Rambow F, Bechadergue A, Luciani F, et al.Regulation of melanoma progression through the TCF4/miR-125b/NEDD9 cascade[J]. J Invest Dermatol, 2016, 136(6): 1229-1237.
[24] Manfè V, Biskup E, Willumsgaard A, et al.cMyc/miR-125b-5p signalling determines sensitivity to bortezomib in preclinical model of cutaneous T-cell lymphomas[J]. PLoS One, 2013, 8(3): e59390.
[25] Zeng CW, Zhang XJ, Lin KY, et al.Camptothecin induces apoptosis in cancer cells via microRNA-125b-mediated mitochondrial pathways[J]. Mol Pharmacol, 2012, 81(4): 578-586.
[26] Lin KY, Ye H, Han BW, et al.Genome-wide screen identified let-7c/miR-99a/miR-125b regulating tumor progression and stem-like properties in cholangiocarcinoma[J]. Oncogene, 2016, 35(26): 3376-3386.
[27] Zhang L, Ge Y, Fuchs E. miR-125b can enhance skin tumor initiation and promote malignant progression by repressing differentiation and prolonging cell survival[J]. Gene Dev, 2014, 28(22): 2532-2546.
[28] Semenza GL.Targeting HIF-1 for cancer therapy[J]. Nat Rev Cancer, 2003, 3(10): 721-732.
[29] Dhillon AS, Hagan S, Rath O, et al.MAP kinase signalling pathways in cancer[J]. Oncogene, 2007, 26(22): 3279-3290.
[30] Xue C, Yao Q, Gu X, et al.Evolving cognition of the JAK-STAT signaling pathway: autoimmune disorders and cancer[J]. Signal Transduct Tar, 2023, 8(1): 204.
[31] Hanahan D, Weinberg RA.Hallmarks of cancer: the next generation[J]. Cell, 2011, 144(5): 646-674.
[32] Cohen EEW, Bell RB, Bifulco CB, et al.The Society for Immunotherapy of cancer consensus statement on immunotherapy for the treatment of squamous cell carcinoma of the head and neck (HNSCC)[J]. J Immunother Cancer, 2019, 7(1): 184.
[33] Philip M, Schietinger A.CD8+ T cell differentiation and dysfunction in cancer[J]. Nat Rev Immunol, 2022, 22(4): 209-223.
[34] Gołabek K, Hudy D, Swietek A, et al.miR-125b-5p, miR-155-3p, and miR-214-5p and target E2F2 gene in oral squamous cell carcinoma[J]. Int J Mol Sci, 2023, 24(7): 6320.