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Research Paper|Volume 11, Issue 15|pp 5646—5665

The long noncoding RNA MIR210HG promotes tumor metastasis by acting as a ceRNA of miR-1226-3p to regulate mucin-1c expression in invasive breast cancer

Xiao-yu Li1, Li-ye Zhou2, Hao Luo1, Qi Zhu1, Liang Zuo1, Gu-yue Liu1, Chu Feng1, Jun-yong Zhao3, Yuan-yuan Zhang4, Xue Li5
  • 1Department of General Surgery, Putuo People’s Hospital of Tongji University, Shanghai, China
  • 2Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA
  • 3Department of General Surgery, Shanghai Tenth People’s Hospital of Tongji University, Shanghai, China
  • 4Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, NC 27101, USA
  • 5Department of Pathology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China
Received: February 9, 2019Accepted: July 31, 2019Published: August 10, 2019
https://doi.org/10.18632/aging.102149

Copyright © 2019 Li et al. This is an open-access article distributed under the terms of the Creative Commons Attribution (CC BY) 3.0 License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Background: Long noncoding RNAs have been known to be involved in multiple types of malignancies, including invasive breast cancer (IBC). This study aimed to explore the role of long noncoding RNAs in IBC and elucidate the potential molecular mechanisms.

Methods: Using TCGA microarray data analysis, we identified a long noncoding RNA, MIR210HG, highly expressed in IBC. Kaplan-Meier method and the log-rank test were used for survival analysis. The gain-of-function experiments were performed to assess the function of MIR210HG in IBC invasion and migration in both in vitro and in vivo settings. Bioinformatic analysis as well as luciferase reporter assay, rescue experiments and western blot assay revealed the mode of action of MIR210HG.

Results: The aberrantly enhanced MiR210HG expression predicted poor prognosis and lower survival rate. Knockdown of MiR210HG suppressed IBC cell invasion and metastasis both in vitro and in vivo. MiR-1226-3p was identified and validated to be the target miRNA of MiR210HG. Furthermore, MiR210HG functions as a competing endogenous RNAs (ceRNA) which sponges miR-1226-3p, therefore upregulates the expression of mucin1 (MUC1-C).

Conclusions: Our study demonstrated that MiR210HG sponges miR-1226-3p to facilitate invasive breast cancer cell invasion and metastasis by regulating mucin-1c and EMT pathway, revealing the oncogenic role of MiR210HG in IBC cells.