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
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
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DOI：
10.18632/aging.102149
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发表时间：
2019-08-15
期刊：
影响因子：
5.2
通讯作者：
Li, Xue
中科院分区：
文献类型：
--
作者：
Li, Xiao-yu;Zhou, Li-ye;Li, Xue
背景：已知长链非编码RNA参与多种类型的恶性肿瘤，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，并阐明其可能的分子机制。方法：利用TCGA基因芯片分析，我们发现了一个在IBC中高表达的长链非编码RNA MIR 210 HG。生存分析采用Kaplan-Meier法和log-rank检验。进行功能获得实验以评估MIR 210 HG在体外和体内环境中在IBC侵袭和迁移中的功能。生物信息学分析、荧光素酶报告基因检测、拯救实验和western blot分析揭示了miR 210 HG的作用机制。MiR 210 HG的敲低抑制IBC细胞在体外和体内的侵袭和转移。MiR-1226- 3 p被鉴定并验证为MiR 210 HG的靶miRNA。结论：miR-1226- 3 p是miR-1226- 3 p的竞争性内源性RNA（ceRNA），miR-1226- 3 p通过调节MUC 1-C的表达，促进浸润性乳腺癌细胞的侵袭和转移，提示miR-1226- 3 p在IBC细胞中的致癌作用。
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.