MicroRNA-373 Inhibits Cell Proliferation and Invasion via Targeting BRF2 in Human Non-small Cell Lung Cancer A549 Cell Line.
- Author:
Lei WANG
1
;
Junfeng QU
;
Li ZHOU
;
Fei LIAO
;
Ju WANG
Author Information
- Publication Type:Original Article
- Keywords: miR-373; BRF2; Non-small cell lung carcinoma; Cell proliferation; Cell migration inhibition; Epithelial-mesenchymal transition
- MeSH: Blotting, Western; Cadherins; Carcinoma, Non-Small-Cell Lung*; Cell Cycle; Cell Line*; Cell Migration Inhibition; Cell Proliferation*; Down-Regulation; Epithelial-Mesenchymal Transition; Humans*; In Vitro Techniques; Methods; MicroRNAs; Prognosis; Real-Time Polymerase Chain Reaction; RNA, Small Interfering; Snails; Up-Regulation
- From:Cancer Research and Treatment 2018;50(3):936-949
- CountryRepublic of Korea
- Language:English
- Abstract: PURPOSE: The purpose of this study was to investigate the biological role and mechanism of miR-373 targeting of TFIIB-related factor 2 (BRF2) in the regulation of non-small cell lung cancer (NSCLC) cells. MATERIALS AND METHODS: miRNA microarray chip analysis of four paired NSCLC and adjacent non-tumor tissues was performed. Quantitative real-time polymerase chain reaction (qRT-PCR) andwestern blotting were used to detect the expression levels of miR-373 and BRF2 in NSCLC tissues and cell lines. The dual-luciferase reporter method was performed to determine if BRF2 is a target of miR-373. MTT, wound-healing, Transwell, and flow cytometric assays were conducted to examine the proliferation, migration, invasion, and cell cycle progression of NSCLC A549 cells, respectively; western blotting was used to detect the expression of epithelial-mesenchymal transition (EMT)–related proteins. RESULTS: The miRNA microarray chip analysis demonstrated that miR-373 was down-regulated in NSCLC tissues, and this result was confirmed by qRT-PCR. Additionally, miR-373 was confirmed to target BRF2. Moreover, miR-373 expression was inversely correlated with BRF2 expression in NSCLC tissues and cell lines; both miR-373 down-regulation and BRF2 up-regulation were strongly associated with the clinicopathological features and prognosis of NSCLC patients. In vitro, overexpression of miR-373 markedly inhibited cell proliferation, migration, and invasion; up-regulated the expression of E-cadherin; and down-regulated the expression of N-cadherin and Snail in A549 cell. Knockdown BRF2 by siRNA resulted in effects similar to those caused by overexpression of miR-373. CONCLUSION: MiR-373 is decreased in NSCLC, and overexpression of miR-373 can suppress cell EMT, and inhibit the proliferation, migration, and invasion of NSCLC A549 cells by targeting BRF2.
