长链非编码 RNA-ROR/miR-145 轴通过靶向 ZEB2 诱导上皮-间充质转化促进肝癌的侵袭和转移。

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

机构信息

Department of Medical Oncology, Jinling Hospital, Medical School of Nanjing University, Nanjing, 210002, Jiangsu Province, China.

Animal Core Facility of Nanjing Medical University, Nanjing, Jiangsu, China.

出版信息

Sci Rep. 2017 Jul 5;7(1):4637. doi: 10.1038/s41598-017-04113-w.

DOI:10.1038/s41598-017-04113-w

PMID:28680141

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5498629/

Abstract

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.

摘要

研究表明，长链非编码 RNA（lncRNA）在肿瘤的发生发展中发挥着重要作用。LincRNA-ROR（linc-ROR）在多种人类癌症中促进肿瘤进展，包括肝细胞癌（HCC）。然而，linc-ROR 在 HCC 转移中的作用及其潜在机制仍未完全阐明。本研究表明，linc-ROR 在 HCC 组织中上调，高水平的 linc-ROR 表达预示着预后不良。功能上，linc-ROR 显著诱导上皮-间充质转化（EMT），增加 HCC 细胞的体外侵袭和体内转移。机制上，linc-ROR 作为 miR-145 的海绵，解除对靶基因 ZEB2 的抑制表达，从而诱导 EMT 并促进 HCC 转移。综上所述，我们的研究表明 linc-ROR 作为一种有潜力的治疗靶点，可用于治疗侵袭性和转移性 HCC。