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微小RNA-192-5p通过激活MEK/ERK信号通路调控胆管癌细胞的增殖与凋亡。

MiR-192-5p regulates the proliferation and apoptosis of cholangiocarcinoma cells by activating MEK/ERK pathway.

作者信息

Tang Chaofeng, Yuan Peng, Wang Jian, Zhang Yubo, Chang Xiaowei, Jin Dong, Lei Peng, Lu Zhenhui, Chen Bendong

机构信息

Department of Hepatobiliary Surgery, General Hospital of Ningxia Medical University, No. 804 Shengli South Street, Xingqing District, Yinchuan, 750001 Ningxia Province China.

Department of Special Ward of Surgery, Shanxi Cancer Hospital, Taiyuan, 030013 Shanxi Province China.

出版信息

3 Biotech. 2021 Feb;11(2):99. doi: 10.1007/s13205-021-02650-w. Epub 2021 Jan 28.

DOI:10.1007/s13205-021-02650-w
PMID:33552829
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7843823/
Abstract

OBJECTIVE

Cholangiocarcinoma (CCA) is the second most common liver cancer, characterized by late diagnosis and fatal outcome. Although miR-192-5p has been shown to have a vital role in various cancers, its role in CCA is unknown. Here, we investigated the role of miR-192-5p in CCA cell proliferation and apoptosis, and elucidated its potential mechanism of action.

METHODS

The miR-192-5p expression in CCA tissues and cell lines was detected by real-time quantitative reverse transcription-polymerase chain reaction. Cell proliferation was analyzed using the cell counting Kit-8 and 5-bromodeoxyuridine staining assays, while apoptosis was examined by flow cytometry and the terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick-end labeling assay. Western blot analysis was used to measure the expression of cell proliferation and apoptosis-related proteins, as well as MEK/ERK signaling pathway-related proteins.

RESULTS

MiR-192-5p was highly expressed in CCA tissues and cell lines. Overexpression of miR-192-5p significantly promoted CCA proliferation, and inhibited apoptosis. The MEK inhibitor, PD98059, reversed these miR-192-5p-induced effects on MEK/ERK signaling-associated protein expression, proliferation promotion, and apoptosis inhibition in TFK-1 cells.

CONCLUSION

MiR-192-5p promotes proliferation and suppressed apoptosis of CCA cells via the MEK/ERK pathway, which may be a potential therapeutic strategy for CCA treatment.

摘要

目的

胆管癌(CCA)是第二常见的肝癌,其特征为诊断较晚且预后不良。尽管miR-192-5p已被证明在多种癌症中发挥重要作用,但其在CCA中的作用尚不清楚。在此,我们研究了miR-192-5p在CCA细胞增殖和凋亡中的作用,并阐明了其潜在的作用机制。

方法

采用实时定量逆转录-聚合酶链反应检测CCA组织和细胞系中miR-192-5p的表达。使用细胞计数试剂盒-8和5-溴脱氧尿苷染色试验分析细胞增殖,通过流式细胞术和末端脱氧核苷酸转移酶脱氧尿苷三磷酸缺口末端标记试验检测细胞凋亡。蛋白质免疫印迹分析用于检测细胞增殖和凋亡相关蛋白以及MEK/ERK信号通路相关蛋白的表达。

结果

miR-192-5p在CCA组织和细胞系中高表达。miR-192-5p的过表达显著促进CCA增殖,并抑制细胞凋亡。MEK抑制剂PD98059可逆转miR-192-5p对TFK-1细胞中MEK/ERK信号相关蛋白表达、增殖促进和凋亡抑制的诱导作用。

结论

miR-192-5p通过MEK/ERK途径促进CCA细胞增殖并抑制其凋亡,这可能是CCA治疗的一种潜在策略。

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