MiR-3194-3p Inhibits Breast Cancer Progression by Targeting Aquaporin1.

Min Wei,Hailang Yu,Huimin Zhu,Cuixia Cai,Rui Gao,Xuhua Liu

doi:10.3389/fonc.2020.01513

Abstract

Increasing evidence indicates that the Aquaporin1 (AQP1) aberrant expression may be related to a wide variety of human cancers, including breast cancer (BC). In the present study, we explore the effects and possible mechanism of miR-3194-3p on the biological behaviors of BC. At first, miR-3194-3p is found to modulate AQP1 expression targeting the 3′-UTR using miRNA target prediction algorithms. MiR-3194-3p expression is markedly downregulated, and AQP1 expression is upregulated in BC tissues compared with adjacent normal breast tissues. Moreover, the differential expression of miR-3194-3p and AQP1 are observed in four BC cells with different malignancy degree. Meanwhile, a significant negative correlation between AQP1 and miR-3194-3p expressions in tumor tissues from 30 BC patients is revealed. miR-3194-3p mimic remarkably inhibits cell proliferation, migration, and invasion as well as promotes apoptosis in MDA-MB-231 cells while miR-3194-3p inhibitors exert an opposite role in MCF-7 cells. Dual-luciferase reporter system demonstrates that AQP1 is a direct target gene of miR-3194-3p. Overexpression of AQP1 by pBABE-puro-AQP1 vector partially abrogates the effect of miR-3194-3p mimic in MDA-MB-231 cells. In short, our results suggest that miR-3194-3p suppresses BC cell proliferation, migration, and invasion by targeting AQP1, providing a novel insight into BC tumorigenesis and treatment.

Highlights

The incidence and mortality of breast cancer (BC) have been high among female malignant tumors, which seriously threatens the health of women worldwide [1, 2]
Spearman’s correlation analysis found a significant negative correlation between the expression levels of miR-3194-3p and AQP1 mRNA in BC tissues (Figure 1F). These results suggest that miR-3194-3p and AQP1 expressions are closely involved in BC progression
Accumulating research has found that AQP1 can affect multiple important biological processes, including angiogenesis, wound healing, tumor metastasis, and invasion, etc

Summary

Introduction

The incidence and mortality of breast cancer (BC) have been high among female malignant tumors, which seriously threatens the health of women worldwide [1, 2]. Aquaporin (AQP1) is a kind of membrane channel protein widely existing in endothelial and epithelial cells of human tissues, which can efficiently and transport water molecules [4]. A growing number of studies have found that AQP1’s function is not limited to transporting water molecules; it is closely related to a wide variety of tumors, including tumors of brain, prostate, breast, ovary, colon, and lung [5]. In BC, AQP1 overexpression is significantly associated with poor prognosis in aggressive breast cancer [9]. EstevaFont et al found that AQP1 deficiency reduces vessel density and lowers lung metastases in mice

Methods

Results

Conclusion