LncRNA HOTAIR epigenetically suppresses miR-122 expression in hepatocellular carcinoma via DNA methylation.
LncRNA HOTAIR epigenetically suppresses miR-122 expression in hepatocellular carcinoma via DNA methylation.
复制标题
长链非编码RNA（lncRNA）HOTAIR通过DNA甲基化在表观遗传学上抑制肝细胞癌中miR - 122的表达。
DOI：
10.1016/j.ebiom.2018.08.055
复制
发表时间：
2018-10
期刊：
影响因子：
11.1
通讯作者：
Zhou J
中科院分区：
文献类型：
--
作者：
Cheng D;Deng J;Zhang B;He X;Meng Z;Li G;Ye H;Zheng S;Wei L;Deng X;Chen R;Zhou J
MicroRNA-122（miR-122）是一种重要的肝脏特异性miRNA，在肝细胞癌（HCC）中常被抑制，并与预后不良相关。长链非编码RNA（lncRNA）HOTAIR已被证实在包括HCC在内的多种癌症中作为癌基因起作用。然而，HOTAIR和miR-122在HCC中的关系在很大程度上仍然未知。我们研究了HOTAIR和miR-122在HCC细胞模型和异种移植小鼠模型中的功能。HOTAIR和miR-122之间的调控网络在HOTAIR过表达或敲低后进一步检测。分析miR-122启动子区DNA甲基化状态以及DNMTs、EZH 2和Cyclin G1的表达水平。在这项研究中，我们发现HOTAIR在HCC中高表达而miR-122被抑制，并且HOTAIR负调控HCC细胞中miR-122的表达。此外，HOTAIR的敲低在体外显著抑制HCC细胞增殖并诱导细胞周期停滞，并且通过上调miR-122表达来抑制体内致瘤性。从机制上讲，CpG岛位于miR-122启动子区域。HOTAIR通过DNMT介导的DNA甲基化表观遗传抑制miR-122表达此外，HOTAIR通过EZH 2上调DNMT表达。此外，HOTAIR诱导的miR-122抑制直接重新激活癌基因Cyclin G1表达。总的来说，我们的研究结果表明，HOTAIR通过DNA甲基化表观遗传抑制miR-122的表达，导致Cyclin G1的激活和促进HCC的致瘤性，这为HOTAIR通过抑制miR-122介导的肝癌发生机制提供了新的见解。HOTAIR在肝癌中高度表达，并负调节肝癌细胞中miR-122的表达。HOTAIR通过下调miR-122表达促进HCC细胞增殖和肿瘤生长。HOTAIR通过DNMT介导的DNA甲基化表观遗传抑制miR-122表达HOTAIR通过EZH 2上调DNMT表达。HOTAIR通过抑制miR-122增加细胞周期蛋白G1的表达。
MicroRNA-122 (miR-122), a pivotal liver-specific miRNA, is frequently repressed in hepatocellular carcinoma (HCC) and associated with poor prognosis. Long non-coding RNA (lncRNA) HOTAIR has been proved to function as an oncogene in multiple cancers including HCC. However, the relationship between HOTAIR and miR-122 in HCC remains largely unknown. We investigated the function of HOTAIR and miR-122 in HCC cell models and a xenograft mouse model. The regulatory network between HOTAIR and miR-122 was further detected following overexpression or knockdown of HOTAIR. DNA methylation status of miR-122 promoter region, as well as expression levels of DNMTs, EZH2 and Cyclin G1 were analyzed. In this study, we found that HOTAIR was highly expressed whereas miR-122 was suppressed in HCC, and HOTAIR negatively regulated miR-122 expression in HCC cells. Furthermore, knockdown of HOTAIR dramatically inhibited HCC cell proliferation and induced cell cycle arrest in vitro and suppressed tumorigenicity in vivo by upregulating miR-122 expression. Mechanistically, a CpG island was located in the miR-122 promoter region. HOTAIR epigenetically suppressed miR-122 expression via DNMTs-mediated DNA methylation. Moreover, HOTAIR upregulated DNMTs expression via EZH2. In addition, suppression of miR-122 induced by HOTAIR directly reactivated oncogene Cyclin G1 expression. Collectively, our results suggest that HOTAIR epigenetically suppresses miR-122 expression via DNA methylation, leading to activation of Cyclin G1 and promotion of tumorigenicity in HCC, which provide new insight into the mechanism of HOTAIR-mediated hepatocarcinogenesis via suppressing miR-122. HOTAIR is highly expressed in HCC, and negatively regulates miR-122 expression in HCC cells. HOTAIR increased HCC cell proliferation and tumor growth through downregulating miR-122 expression. HOTAIR epigenetically suppressed miR-122 expression via DNMTs-mediated DNA methylation. HOTAIR upregulated DNMTs expression via EZH2. HOTAIR increased cyclin G1 expression through repressing miR-122.
登录
查看更多内容
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
25.7
作者：
Li, Zhen-Ya;Xi, Yang;Liang, Chih-Chuan
通讯作者：
Liang, Chih-Chuan
影响因子：
3.8
作者：
Lu, Lingeng;Zhu, Gongjian;Yu, Herbert
通讯作者：
Yu, Herbert
影响因子：
50.3
作者：
Kim E;Kim M;Woo DH;Shin Y;Shin J;Chang N;Oh YT;Kim H;Rheey J;Nakano I;Lee C;Joo KM;Rich JN;Nam DH;Lee J
通讯作者：
Lee J
影响因子：
5.6
作者：
Ding C;Cheng S;Yang Z;Lv Z;Xiao H;Du C;Peng C;Xie H;Zhou L;Wu J;Zheng S
通讯作者：
Zheng S