MicroRNA-490 inhibits tumorigenesis and progression in breast cancer

被引:34
作者
Zhao, Lin [1 ]
Zheng, Xin-Yu [1 ,2 ]
机构
[1] China Med Univ, Hosp 1, Dept Breast Surg, 155 Nanjing North St, Shenyang 110001, Peoples R China
[2] China Med Univ, Canc Inst China, Lab 1, Shenyang, Peoples R China
来源
ONCOTARGETS AND THERAPY | 2016年 / 9卷
基金
中国国家自然科学基金;
关键词
breast cancer; miR-490-3p; RhoA; tumorigenesis and progression; CELL-GROWTH; RHOA; PROLIFERATION; RECOGNITION; APOPTOSIS; MIGRATION; GTPASES;
D O I
10.2147/OTT.S100037
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
MicroRNAs are consistently reported to regulate gene expression in all cancer cell types by modulating a wide range of biological processes, including cell proliferation, differentiation, and apoptosis, which are associated with tumor development and progression. Previous studies have revealed that miR-490-3p regulates cell proliferation and apoptosis in cancers, such as hepatocellular carcinoma, lung cancer, bladder cancer, and ovarian carcinoma. In this study, we explored the hitherto unrevealed role of miR-490-3p in breast cancer. We tested miR-490-3p expression in breast cancer tissue and paracarcinoma tissue using reverse transcription-polymerase chain reaction. We also transfected the human breast cancer cell lines MCF-7 and T47D with miR-490-3p; subsequently, we determined the cell phenotype and the expression of Ras homolog gene family member A (RhoA), Bcl-xL, matrix metalloproteinase-9, and P70S6K (P70S6 kinase). Dual-luciferase reporter assay and a xenograft mouse model were used to reveal the roles of miR-490-3p and its target gene RHOA. We found that the levels of miR-490-3p were lower in the breast cancer tissue than in the paracarcinoma tissues. The overexpression of miR-490-3p suppressed breast cancer cell proliferation and promoted early stage apoptosis. Western blotting results revealed that the miR-490-3p overexpression reduced RhoA, Bcl-XL, matrix metalloproteinase-9, and P70S6K protein expression. The dual-luciferase reporter assay confirmed that RhoA is a target of miR-490-3p. The xenograft mouse model confirmed that miR-490-3p overexpression suppressed tumor growth and reduced RhoA expression. Our results indicate that miR-490-3p acts as oncosuppressive microRNA to inhibit breast cancer tumorigenesis and progression by targeting RhoA directly. It may contribute to breast cancer diagnosis and treatment.
引用
收藏
页码:4505 / 4516
页数:12
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