Objective: To investigate the correlations of the methylation statuses of miR-200b in tissue and serum of bladder cancer(BLCA) patients with epithelial-mesenchymal transition(EMT) and clinical pathological features. Methods: From September 2018 to October 2020, the tumor tissue samples and blood samples of 126 BLCA patients who underwent surgery(BLCA group) in our hospital were collected. And 63 samples of normal bladder mucosa tissues were selected as the control group. The methylation statuses of miR-200b in tissue and serum samples were detected by methylation-specific PCR. Quantitative real-time fluorescent PCR was used to detect the expressions of serum miR-200b. Based on The Cancer Genome Atlas(TCGA) database, the relationship between miR-200b in tissues of BLCA patients and EMT related transcription factors was analyzed. Results: The methylation rate of miR-200b in BLCA group was higher than that in the control group(P<0.05), and the expression of miR-200b was lower than that in the control group(P<0.05). For BLCA patients, the results of miR-200b methylation statuses in tumor tissue and serum samples were consistent(Kappa=0.715, P<0.001), and the expression level of serum miR-200b in serum miR-200b methylation subgroup was significantly lower than that in unmethylation subgroup(P<0.05). The patients with muscle-invasive, distant metastasis or middle-low grade bladder cancer had higher methylation rates of tissue and serum miR-200b, and the patients with lymph node metastasis also had higher methylation rates of serum miR-200b(P<0.05). Based on TCGA database, the expressions of miR-200b were negatively correlated with the expression of hyaluronan synthases-2, zinc finger E-box-binding homeobox(ZEB) 1 and ZEB2 proteins expressions in BLCA patients(P<0.05). Conclusion: The methylation statuses of miR-200b are common in tissue and serum samples of BLCA patients, which are related to the muscle-invasion, distant metastasis and the degree of differentiation. Its mechanism may be through up-regulating the expression of EMT related transcription factors, thus activating the EMT process. |
[1] MARTINEZ RODRIGUEZ R H, BUISAN RUEDA O, IBARZ L.Bladder cancer:present and future[J].Med Clin(Barc), 2017, 149(10):449-455.
[2] DONGRE A, WEINBERG R A.New insights into the mechanisms of epithelial-mesenchymal transition and implications for cancer[J].Nat Rev Mol Cell Biol, 2019, 20(2):69-84.
[3] 李国彬, 张占成, 王新颜, 等.上调miR-200b对人喉癌Hep-2细胞增殖、迁移和侵袭能力的影响[J].山东大学耳鼻喉眼学报, 2018, 21(4):53-57.
[4] 何楠, 吴共发, 赵海燕, 等.结直肠癌中miR-200家族启动子甲基化状态分析[J].临床与实验病理学杂志, 2014, 30(10):1081-1085.
[5] SIRACUSANO S, RIZZETTO R, PORCARO A B.Bladder cancer genomics[J].Urologia, 2020, 87(2):49-56.
[6] 王猛, 滕晓东.肌层浸润性膀胱癌的分子分型研究进展[J].中华病理学杂志, 2017, 45(6):439-442.
[7] 李攀, 曹金龙, 姚志强, 等.肌层与非肌层浸润性膀胱癌差异基因的生物信息学分析[J].重庆医科大学学报, 2021, 44(1):57-64.
[8] SOUSA M C D, DOLICKA D, GJORGJIEVA M, et al.Deciphering miRNAs' action through miRNA editing[J].Int J Mol Sci, 2019, 20(24):6249-6270.
[9] RAJIC J, DINIC S, USKOKOVIC A, et al.DNA methylation of miR-200 clusters promotes epithelial to mesenchymal transition in human conjunctival epithelial cells[J].Exp Eye Res, 2020, 197(8):108047.
[10] ARUNKUMAR G, DEVA MAGENDHRA RAO A K, MANIKANDAN M, et al.Dysregulation of miR-200 family microRNAs and epithelial-mesenchymal transition markers in oral squamous cell carcinoma[J].Oncol Lett, 2018, 15(1):649-657.
[11] YEH T S, WANG F, CHEN T C, et al.Expression profile of microRNA-200 family in hepatocellular carcinoma with bile duct tumor thrombus[J].Ann Surg, 2014, 259(2):346-354.
[12] 王暑光, 王静成, 孙钰, 等.丝裂霉素C调控miR-200b启动子甲基化诱导成纤维细胞凋亡[J].实用医学杂志, 2017, 33(6):876-879.
[13] TAMAGAWA S, ENOMOTO K, GUNDUZ E, et al.MicroRNA 200b promotes mesenchymal-to-epithelial transition in anaplastic thyroid carcinoma[J].Oncol Lett, 2020, 20(4):3-10. |