MicroRNA-16-5p overexpression suppresses proliferation and invasion as well as triggers apoptosis by targeting VEGFA expression in breast carcinoma.

Yunhui Qu,Yuqiong Liu,Hongtao Liu,Xiaojuan Wang,Shenglei Li,Qianqian Lou,Huixiang Li,Xiaqing Zhang,Xinquan Lv,Min Zhang,Yuenan Li

doi:10.18632/oncotarget.20398

Yunhui Qu, Yuqiong Liu + Show 9 more

Open Access

https://doi.org/10.18632/oncotarget.20398

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Abstract

MicroRNAs (miRNAs), a class of small noncoding RNA molecules, can manipulate the expressions of endogenous tumor-related genes, and are implicated in the development and progression of a wide type of tumors. In this study, the investigation from real-time quantitative PCR revealed that miRNA-16-5p was downregulated in breast carcinoma tissues and cells, coupled with the elevations of HIF-α and VEGFA protein expressions, compared with normal tissues. Lentiviral armed with miR-16-5p markedly increased the miR-16-5p levels in MCF-7 and MDA-MB-231 cells, compared to blank and NC groups, and miR-16-5p overexpression significantly inhibited the proliferation and colony formation in MCF-7 and MDA-MB-231 cells. Besides, miR-16-5p upregulation markedly induced apoptosis and reduced invasion ability in MCF-7 and MDA-MB-231 cells. Notably, VEGFA was direct target of miR-16-5p. Stepwise investigation from in vitro and in vivo experiments demonstrated that miR-16-5p overexpression suppressed tumor growth and reduced HIF-α and VEGFA expressions in breast carcinoma cells and nude mice tumor tissues. These findings provide novel insights into molecular mechanism involved in the roles of miR-16-5p in tumor development and progression of breast carcinoma, and thus manipulation of miR-16-5p may be a novel potential therapeutic target for future therapies of the patients with breast carcinoma.

Highlights

Breast carcinoma, a kind of highly heterogeneous disease characterized by a wide variety of molecular and pathologic diversity [1, 2], is one of the most frequently diagnosed women tumor types worldwide [3]
We found that the expression of miR-16-5p in breast carcinoma tissues was significantly lower than that in paired normal tissues (P < 0.05) (Figure 1A)
More and more evidence has demonstrated that miRNAs have a wide variety of biological functions mainly implicated in several cell signaling pathways essential to tumor development and progression, including proliferation, apoptosis, differentiation, invasion and metastasis [18, 19], which mainly function either as oncogenes or tumor suppressor genes [20, 21], which will open up new opportunities for a large number of tumors

Summary

Introduction

A kind of highly heterogeneous disease characterized by a wide variety of molecular and pathologic diversity [1, 2], is one of the most frequently diagnosed women tumor types worldwide [3]. More than 90% of the patients with breast carcinoma died due to metastasis [8]. These features will lead to the results that the different patients with breast carcinoma have different prognosis and response to tumor therapies [9]. It is imperative to seek for novel molecular target for the diagnosis and therapy of the patients with breast carcinoma

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Results

Conclusion