microRNA-448 inhibits the progression of non-small-cell lung cancer through regulating IRS2

被引:25
作者
Gao, Jie [2 ]
Feng, Xiaojing [3 ]
Wang, Fang [4 ]
Wang, Junlan [5 ]
Wang, Hongmei [6 ]
Li, Hua [7 ]
Zhang, Weiwei [8 ]
Hao, Lijun [6 ]
Shi, Zhiming [1 ]
机构
[1] Hebei Univ Engn, Dept Pathol, Affiliated Hosp, Handan 056002, Hebei, Peoples R China
[2] Hebei Univ Engn, Affiliated Hosp, Dept CT, Handan, Hebei, Peoples R China
[3] Handan Peace Hosp, Handan, Hebei, Peoples R China
[4] Hebei Univ Engn, Affiliated Hosp, Dept Respirat, Handan, Hebei, Peoples R China
[5] Second Hosp Handan City, Dept CT, Handan, Hebei, Peoples R China
[6] Staff Hosp, Handan Iron & Steel Grp Co, Handan, Hebei, Peoples R China
[7] Hebei Univ Engn, Affiliated Hosp, Dept Neurol, Handan, Hebei, Peoples R China
[8] Handan Maternal & Child Hlth Hosp, Handan, Peoples R China
关键词
epithelial-to-mesenchymal transition; IRS2; metastasis; miR-448; non-small-cell lung cancer; proliferation; EPITHELIAL-MESENCHYMAL TRANSITION; METASTASIS; INVASION; GROWTH; TUMORIGENESIS; PROTEINS; EMT;
D O I
10.1002/jcb.28619
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
Recently, microRNA-448 (miR-448) has been reported to be a tumor-associated miRNA in many human cancers. In this study, we investigated the function of miR-448 in non-small-cell lung cancer (NSCLC) progression and confirmed the relationship between miR-448 and insulin receptor substrates 2 (IRS2). First, downregulation of miR-448 and upregulation of IRS2 were detected in NSCLC using the quantitative real-time polymerase chain reaction (qRT-PCR) assay. Furthermore, the MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assay showed that miR-448 inhibited cell viability in NSCLC. Transwell and Western blot assays indicated that the upregulation of miR-448 inhibited cell metastasis and epithelial-to-mesenchymal transition (EMT) in NSCLC. And it was found that overexpression of miR-448 reduced the adhesion of A549 cells to HUVEC cells using the adhesion assay. Furthermore, the dual luciferase assay indicated that miR-448 directly targeted IRS2 in NSCLC. In addition, it was found that IRS2 silencing had an inhibitory effect on the progression of NSCLC, and the upregulation of IRS2 partially impaired the inhibitory effect of miR-448 in NSCLC. Briefly, overexpression of miR-448 inhibited cell proliferation, metastasis, and EMT by suppressing IRS2 expression in NSCLC.
引用
收藏
页码:13453 / 13463
页数:11
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