miR-195-5p exerts tumor-suppressive functions in human lung cancer cells through targeting TrxR2

被引:17
作者
Bu, Lina [1 ,2 ]
Tian, Yingxuan [3 ]
Wen, Hongqing [1 ]
Jia, Weihong [1 ]
Yang, Shuanying [2 ]
机构
[1] Northwest Univ, Xian 3 Hosp, Affiliated Hosp, Dept Resp & Crit Care Med, Xian 710018, Peoples R China
[2] Xi An Jiao Tong Univ, Affiliated Hosp 2, Dept Resp & Crit Care Med, Xian 710004, Peoples R China
[3] Shaanxi Prov Peoples Hosp, Dept Geriatr Resp, Xian 710068, Peoples R China
基金
中国国家自然科学基金;
关键词
miR-195-5p; TrxR2; lung adenocarcinoma; tumor suppression; MICRORNAS;
D O I
10.1093/abbs/gmaa159
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
miR-195-5p has been widely explored in various cancers and is considered as a tumor-suppressive microRNA. However, its roles in human lung cancer pathogenesis are not fully elucidated. In this study, we aimed to explore how miR-195-5p is involved in malignant behaviors of lung adeno-carcinoma (LUAD) cells. miR-195-5p expression was examined in the tumor tissues of patients with LUAD and human LUAD cell lines including A549 and PC-9. Thioredoxin reductase 2 (TrxR2) was predicted to be an mRNA target of miR-195-5p using online tools and validated by the Dual-Luciferase Reporter Assay. Lentivirus infection was used for gene overexpression, while gene knockdown was achieved by RNA interference. Cell proliferation was determined by Cell Counting Kit-8 and 5-ethynyl-2'-deoxyuridine methods, and cell migration and invasion were assayed with transwell experiments. Cell apoptosis was determined by annexin V staining-based flow cytometry. The antitumor effects of miR-195-5p were also evaluated in nude mice xenografted with A549 cells. We found that miR-195-5p was lowly expressed in human LUAD cells, and its overexpression markedly suppressed cell proliferation, migration, and invasion and increased the apoptosis of LUAD cells in vitro. TrxR2 knockdown phenocopied the tumor-suppressive effects of miR-195-5p overexpression, while simultaneous TrxR2 overexpression remarkably reversed the effects of miR-195-5p overexpression on malignant behaviors of A549 and PC-9 cells. Additionally, miR-195-5p overexpression inhibited the growth of xenografted A549 tumor in nude mice. Our work verified that miR-195-5p exerts tumor-suppressive functions in LUAD cells through targeting TrxR2 and suggested that the miR-195-5p/TrxR2 axis is a potential biomarker for LUAD therapy.
引用
收藏
页码:189 / 200
页数:12
相关论文
共 50 条
[1]   miR-15a and miR-16 Are Implicated in Cell Cycle Regulation in a Rb-Dependent Manner and Are Frequently Deleted or Down-regulated in Non-Small Cell Lung Cancer [J].
Bandi, Nora ;
Zbinden, Samuel ;
Gugger, Mathias ;
Arnold, Marlene ;
Kocher, Verena ;
Hasan, Lara ;
Kappeler, Andreas ;
Brunner, Thomas ;
Vassella, Erik .
CANCER RESEARCH, 2009, 69 (13) :5553-5559
[2]   MicroRNAs: Genomics, biogenesis, mechanism, and function (Reprinted from Cell, vol 116, pg 281-297, 2004) [J].
Bartel, David P. .
CELL, 2007, 131 (04) :11-29
[3]  
Bray F, 2018, CA-CANCER J CLIN, V68, P394, DOI [10.3322/caac.21492, 10.3322/caac.21609]
[4]   Inhibition of TrxR2 suppressed NSCLC cell proliferation, metabolism and induced cell apoptosis through decreasing antioxidant activity [J].
Bu, Lina ;
Li, Wei ;
Ming, Zongjuan ;
Shi, Jie ;
Fang, Ping ;
Yang, Shuanying .
LIFE SCIENCES, 2017, 178 :35-41
[5]   MiR-497-5p, miR-195-5p and miR-455-3p function as tumor suppressors by targeting hTERT in melanoma A375 cells [J].
Chai, Li ;
Kang, Xiao-Jing ;
Sun, Zhen-Zhu ;
Zeng, Ming-Feng ;
Yu, Shi-Rong ;
Ding, Yuan ;
Liang, Jun-Qin ;
Li, Ting-Ting ;
Zhao, Juan .
CANCER MANAGEMENT AND RESEARCH, 2018, 10 :989-1003
[6]   Imbalance in redox status is associated with tumor aggressiveness and poor outcome in lung adenocarcinoma patients [J].
da Motta, Leonardo Lisboa ;
Mueller, Carolina B. ;
De Bastiani, Marco A. ;
Behr, Guilherme A. ;
Franca, Fernanda S. ;
da Rocha, Ricardo F. ;
Minotto, Juliane B. ;
Meurer, Rosalva T. ;
Fernandes, Marilda C. ;
Roehe, Adriana ;
Markoski, Melissa M. ;
Andrade, Cristiano F. ;
Castro, Mauro A. A. ;
Klamt, Fabio .
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY, 2014, 140 (03) :461-470
[7]   MicroRNA-195-5p suppresses glucose uptake and proliferation of human bladder cancer T24 cells by regulating GLUT3 expression [J].
Fei, Xiang ;
Qi, Manlong ;
Wu, Bin ;
Song, Yongsheng ;
Wang, Yueping ;
Li, Tingting .
FEBS LETTERS, 2012, 586 (04) :392-397
[8]   Expression profiles of thioredoxin family proteins in human lung cancer tissue: correlation with proliferation and differentiation [J].
Fernandes, Aristi P. ;
Capitanio, Arrigo ;
Selenius, Markus ;
Brodin, Ola ;
Rundlof, Anna-Klara ;
Bjornstedt, Mikael .
HISTOPATHOLOGY, 2009, 55 (03) :313-320
[9]   Targeting microRNAs in cancer: rationale, strategies and challenges [J].
Garzon, Ramiro ;
Marcucci, Guido ;
Croce, Carlo M. .
NATURE REVIEWS DRUG DISCOVERY, 2010, 9 (10) :775-789
[10]  
GIACCONE G, 1992, CANCER RES, V52, pS2732