长链非编码RNA MIR210HG通过作为miR-1226-3p的竞争性内源RNA来调控浸润性乳腺癌中黏蛋白-1c的表达，从而促进肿瘤转移。

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.

作者信息

Li Xiao-Yu, Zhou Li-Ye, Luo Hao, Zhu Qi, Zuo Liang, Liu Gu-Yue, Feng Chu, Zhao Jun-Yong, Zhang Yuan-Yuan, Li Xue

机构信息

Department of General Surgery, Putuo People's Hospital of Tongji University, Shanghai, China.

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.

出版信息

Aging (Albany NY). 2019 Aug 10;11(15):5646-5665. doi: 10.18632/aging.102149.

DOI:10.18632/aging.102149

PMID:31399552

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6710038/

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 and 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 and in . 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.

摘要

背景

长链非编码RNA已被证实参与多种恶性肿瘤，包括浸润性乳腺癌（IBC）。本研究旨在探讨长链非编码RNA在IBC中的作用，并阐明潜在的分子机制。

方法

利用TCGA微阵列数据分析，我们鉴定出一种在IBC中高表达的长链非编码RNA，即MIR210HG。采用Kaplan-Meier法和对数秩检验进行生存分析。进行功能获得实验以评估MIR210HG在体外和体内IBC侵袭和迁移中的功能。生物信息学分析以及荧光素酶报告基因检测、拯救实验和蛋白质印迹分析揭示了MIR210HG的作用模式。

结果

MiR210HG异常增强的表达预示着预后不良和生存率较低。在体外和体内敲低MiR210HG均抑制IBC细胞的侵袭和转移。MiR-1226-3p被鉴定并验证为MiR210HG的靶标miRNA。此外，MiR210HG作为一种竞争性内源性RNA（ceRNA），可吸附miR-1226-3p，从而上调粘蛋白1（MUC1-C）的表达。