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miR-133b 的抑制表明预后不良,并通过 SOX4 促进 OSCC 的进展。

Inhibition of miR-133b indicates poor prognosis and promotes progression of OSCC via SOX4.

机构信息

Department of Oral and Maxillofacial Surgery, The First People's Hospital of Lianyungang, China.

出版信息

Eur Rev Med Pharmacol Sci. 2020 Dec;24(24):12717-12726. doi: 10.26355/eurrev_202012_24170.

DOI:10.26355/eurrev_202012_24170
PMID:33378019
Abstract

OBJECTIVE

Oral squamous cell carcinoma (OSCC) accounts for the first largest proportion of oral and maxillofacial malignancies worldwide. Increasing studies have indicated that miRNAs are involved in the regulation of various tumors, including OSCC. However, the exact role of miR-133b in OSCC has not been fully elucidated. Here, we aimed to explore the effects of miR-133b on the development and progression of OSCC and its related mechanisms.

PATIENTS AND METHODS

Expression of miR-133b in 44 paired OSCC tissues and adjacent normal tissues were detected using quantitative real-time polymerase chain reaction (qRT-PCR). Clinicopathological characteristics were collected from OSCC patients, and the relationship between miR-133b expression and the prognosis of patients was analyzed. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) and colony formation assays were employed to measure the proliferation of OSCC cells transfected with miR-133b inhibitors or mimics. Cell invasion and migration were detected using transwell and Matrigel experiments, respectively. Bioinformatics and Western blot were applied to investigate the possible underlying mechanism of miR-133b in OSCC.

RESULTS

MiR-133b was lowly expressed in OSCC tissues compared to adjacent normal tissues (p<0.05). Lower expression miR-133b indicated a significantly worse prognosis of OSCC patients (p<0.05). Over-expression of miR-133b reduced the growth and metastasis of SCC9 cells (p<0.05). Transfection of miR-133b inhibitors obviously enhanced the proliferation, migration and invasion of TSC-15 cells (p<0.05). SRY-Box Transcription Factor 4 (SOX4) was verified as a specific target for miR-133b. Up- or down-regulation of miR-133b decreased or increased the protein expression level of SOX4 in OSCC, respectively (p<0.05).

CONCLUSIONS

MiR-133b was lowly expressed in OSCC tissues and cell lines. Down-regulation of miR-133b reduced the proliferation, invasion and migration of OSCC cells via regulating SOX4. All our findings suggested that miR-133b could be used as a potential target for the treatment of OSCC.

摘要

目的

口腔鳞状细胞癌(OSCC)占全球口腔颌面部恶性肿瘤的最大比例。越来越多的研究表明,miRNAs 参与了多种肿瘤的调控,包括 OSCC。然而,miR-133b 在 OSCC 中的确切作用尚未完全阐明。本研究旨在探讨 miR-133b 对 OSCC 发生发展的影响及其相关机制。

患者与方法

采用实时定量聚合酶链反应(qRT-PCR)检测 44 对 OSCC 组织及其相邻正常组织中 miR-133b 的表达。收集 OSCC 患者的临床病理特征,分析 miR-133b 表达与患者预后的关系。采用 MTT(3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐)和集落形成实验检测转染 miR-133b 抑制剂或模拟物后 OSCC 细胞的增殖。采用 Transwell 和 Matrigel 实验分别检测细胞侵袭和迁移。应用生物信息学和 Western blot 技术探讨 miR-133b 在 OSCC 中的潜在作用机制。

结果

与相邻正常组织相比,OSCC 组织中 miR-133b 的表达水平较低(p<0.05)。低表达 miR-133b 提示 OSCC 患者预后较差(p<0.05)。过表达 miR-133b 可降低 SCC9 细胞的生长和转移(p<0.05)。转染 miR-133b 抑制剂可明显增强 TSC-15 细胞的增殖、迁移和侵袭(p<0.05)。SRY-Box 转录因子 4(SOX4)被验证为 miR-133b 的特异性靶基因。上调或下调 miR-133b 可分别降低或增加 OSCC 中 SOX4 的蛋白表达水平(p<0.05)。

结论

miR-133b 在 OSCC 组织和细胞系中低表达。下调 miR-133b 通过调控 SOX4 降低 OSCC 细胞的增殖、侵袭和迁移。综上所述,miR-133b 可作为治疗 OSCC 的潜在靶点。

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