Long non-coding RNA MIAT promotes breast cancer progression and functions as ceRNA to regulate DUSP7 expression by sponging miR-155-5p.

Tian Luan,Lihong Wang,Yan Song,Shunheng Zhou,Huilong Cai,Qingyuan Zhang,Shuyuan Wang,Jing Lin,Yue Yang,Weiwei An,Ximei Zhang,Weiguang Yuan

doi:10.18632/oncotarget.19190

Abstract

Long non-coding RNAs (lncRNA) have been reported as key regulators in the progression and metastasis of breast cancer. In this study, we found that the lncRNA myocardial infarction associated transcript (MIAT) expression was upregulated in breast cancer in The Cancer Genome Atlas (TCGA) data sets. We validated that MIAT was higher in breast cancer cell lines and advanced breast tumors than in normal controls. And MIAT overexpression associated with TNM stage and lymphnode metastasis. Knockdown MIAT inhibited breast cancer cell proliferation and promoted apoptosis. Also MIAT downregulation suppressed epithelial-mesenchymal transition (EMT) and decreased migration and invasion in MDA-MB-231 and MCF-7 breast cancer cell lines. More importantly, knockdown MIAT inhibited tumor growth in vivo. Our results suggested that MIAT acted as a competing endogenous RNA (ceRNA) to regulate the expression of dual specificity phosphatase 7 (DUSP7) by taking up miR-155-5p in breast cancer. There were positive correlation between MIAT and DUSP7 expression in breast cancer patients. We conclude that MIAT promotes breast cancer progression and functions as ceRNA to regulate DUSP7 expression by sponging miR-155-5p in breast cancer.

Highlights

Breast cancer is the most common malignancy in women and the incidence increases gradually all over the world [1, 2]
We found that the Long non-coding RNAs (lncRNA) myocardial infarction associated transcript (MIAT) expression was upregulated in breast cancer in The Cancer Genome Atlas (TCGA) data sets
The results revealed that MIAT was upregulated in breast cancer tissues than in normal breast tissues (P

Summary

Introduction

Breast cancer is the most common malignancy in women and the incidence increases gradually all over the world [1, 2]. Emerging evidence has suggested lncRNA as a new class of players involved in the development and progression of cancer [4, 5]. The regulatory roles played by lncRNAs in breast cancer are largely unknown. His groups presented a competing endogenous RNA (ceRNA) hypothesis in 2011 [13], increasing evidence has been provided that lncRNAs as ceRNAs were involved in cancer onset and progression [5, 14]. It has been reported that MIAT regulated microvascular dysfunction through acting as a ceRNA by sponging miR-150-5p [15, 16]. A bioinformatics analysis showed that there were conserved binding sites for both MIAT and the 3′-UTR of DUSP7 mRNA on miR-155-5p. DUSP7 has been shown to be overexpressed in peripheral blood mononuclear cells and bone marrow from patients diagnosed with acute leukemia [19, 20]

Methods

Results

Conclusion