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miR-148a 通过靶向 IGF-IR 抑制 ERK/MAPK 通路抑制口腔鳞状细胞癌进展。

MiR-148a inhibits oral squamous cell carcinoma progression through ERK/MAPK pathway via targeting IGF-IR.

机构信息

Department of Oral and Maxillofacial Surgery, The Chinese PLA General Hospital, Haidian District, Beijing, China.

Department of Stomatology, The 316th Hospital of Chinese People's Liberation Army, Haidian District, Beijing, China.

出版信息

Biosci Rep. 2020 Apr 30;40(4). doi: 10.1042/BSR20182458.

Abstract

OBJECTIVE

The current study aimed to investigate the functional roles and clinical significance of microRNA-148a (miR-148a) in the progression of oral squamous cell carcinoma (OSCC).

METHODS

Relative expression of miR-148a in OSCC cells and tissues were detected using quantitative real-time polymerase chain reaction (qRT-PCR). Chi-square test was performed to estimate the relationship between miR-148a expression and clinical characteristics of OSCC patients. Cell transfection was carried out using Lipofectamine® 2000. Biological behaviors of tumor cells were detected using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and transwell assays. Bioinformatics analysis and luciferase reporter assay were used to identify the target genes of miR-148a. Protein expression was detected through Western blot analysis.

RESULTS

MiR-148a expression was obviously decreased in OSCC tissues and cells, and such down-regulation was closely correlated with lymph node metastasis (P=0.027) and tumor node metastasis (TNM) stage (P=0.001) of OSCC patients. miR-148a overexpression could significantly impair OSCC cell proliferation, migration and invasion in vitro (P<0.05 for all). Insulin-like growth factor-I receptor (IGF-IR) was a potential target of miR-148a. MiR-148a could inhibit ERK/MAPK signaling pathway through targeting IGF-IR.

CONCLUSION

MiR-148a plays an anti-tumor role in OSCC and inhibits OSCC progression through suppressing ERK/MAPK pathway via targeting IGF-IR.

摘要

目的

本研究旨在探讨微小 RNA-148a(miR-148a)在口腔鳞状细胞癌(OSCC)进展中的功能作用和临床意义。

方法

采用实时定量聚合酶链反应(qRT-PCR)检测 OSCC 细胞和组织中 miR-148a 的相对表达。采用卡方检验评估 miR-148a 表达与 OSCC 患者临床特征之间的关系。采用 Lipofectamine®2000 进行细胞转染。采用 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐(MTT)和 Transwell 分析检测肿瘤细胞的生物学行为。采用生物信息学分析和荧光素酶报告基因实验鉴定 miR-148a 的靶基因。采用 Western blot 分析检测蛋白表达。

结果

miR-148a 在 OSCC 组织和细胞中的表达明显下调,这种下调与 OSCC 患者的淋巴结转移(P=0.027)和肿瘤淋巴结转移(TNM)分期(P=0.001)密切相关。miR-148a 过表达可显著抑制 OSCC 细胞的体外增殖、迁移和侵袭(均 P<0.05)。胰岛素样生长因子-I 受体(IGF-IR)是 miR-148a 的一个潜在靶基因。miR-148a 可通过靶向 IGF-IR 抑制 ERK/MAPK 信号通路。

结论

miR-148a 在 OSCC 中发挥抑癌作用,通过靶向 IGF-IR 抑制 ERK/MAPK 通路抑制 OSCC 进展。

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