The lincRNA-ROR/miR-145 axis promotes invasion and metastasis in hepatocellular carcinoma via induction of epithelial-mesenchymal transition by targeting ZEB2.

The lincRNA-ROR/miR-145 axis promotes invasion and metastasis in hepatocellular carcinoma via induction of epithelial-mesenchymal transition by targeting ZEB2.
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DOI:
10.1038/s41598-017-04113-w
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发表时间:
2017-07-05
期刊:
影响因子:
4.6
通讯作者:
Wang R
Wang R
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Li C;Lu L;Feng B;Zhang K;Han S;Hou D;Chen L;Chu X;Wang R

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新的证据表明,长链非编码RNA(lncRNA)在肿瘤的发展中起着关键作用。已知LincRNA-ROR(linc-ROR)促进几种人类癌症(包括肝细胞癌(HCC))中的肿瘤进展。然而,linc-ROR在HCC转移中的作用及其潜在机制仍不清楚。在本研究中,我们发现linc-ROR在HCC组织中上调,linc-ROR高表达水平预示预后不良。在功能上,linc-ROR显着诱导上皮间质转化(EMT),并增加肝癌细胞的体外侵袭和体内转移。在机制上,linc-ROR作为miR-145的海绵,去抑制靶基因ZEB 2的表达,从而诱导EMT并促进HCC转移。总的来说,我们的研究表明linc-ROR作为治疗侵袭性和转移性HCC的重要治疗靶点的潜力。
Emerging evidence show that long noncoding RNAs (lncRNAs) play critical roles in tumor development. LincRNA-ROR (linc-ROR) is known to promote tumor progress in several human cancers, including hepatocellular carcinoma (HCC). Nevertheless, the roles of linc-ROR in HCC metastasis and its underlying mechanisms remain fully unclear. In the present study, we showed that linc-ROR was upregulated in HCC tissues and high linc-ROR expression level predicted poor prognosis. Functionally, linc-ROR significantly induced epithelial-mesenchymal transition (EMT), and increased in vitro invasion and in vivo metastasis of HCC cells. Mechanistically, linc-ROR acted as a sponge for miR-145 to de-repress the expression of target gene ZEB2, thereby inducing EMT and promoting HCC metastasis. Collectively, our research indicates the potential of linc-ROR as a vital therapeutic target for the treatment of aggressive and metastatic HCC.