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长链非编码 RNA SNAI3-AS1 通过调控 UPF1/Smad7 信号通路促进肝癌的增殖和转移。

Long non-coding RNA SNAI3-AS1 promotes the proliferation and metastasis of hepatocellular carcinoma by regulating the UPF1/Smad7 signalling pathway.

机构信息

Department of Gastroenterology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.

出版信息

J Cell Mol Med. 2019 Sep;23(9):6271-6282. doi: 10.1111/jcmm.14513. Epub 2019 Jul 2.

Abstract

Emerging evidence has indicated that deregulation of long non-coding RNAs (lncRNAs) can contribute to the progression of human cancers, including hepatocellular carcinoma (HCC). However, the role and exact mechanism of most lncRNAs in tumours remains largely unknown. In the current study, we found a novel long non-coding RNA termed SNAI3-AS1 which was generally up-regulated in HCC tissues compared with normal control. Higher expression of SNAI3-AS1 was significantly correlated with shorter overall survival of HCC patients. Knockdown of SNAI3-AS1 inhibited the proliferation and metastasis of HCC cells in vitro, whereas overexpression of SNAI3-AS1 promoted the proliferation and metastasis of HCC cells. Further investigations showed that SNAI3-AS1 could affect HCC tumorigenesis by binding up-frameshift protein 1 (UPF1), regulating Smad7 expression and activating TGF-β/Smad pathway. Functionally, SNAI3-AS1 promoted HCC growth and metastasis by inducing tumour epithelial to mesenchymal transition (EMT). Taken together, these findings showed that SNAI3-AS1 promotes the progression of HCC by regulating the UPF1 and activating TGF-β/Smad pathway.

摘要

新出现的证据表明,长非编码 RNA(lncRNA)的失调可能导致包括肝细胞癌(HCC)在内的人类癌症的进展。然而,大多数 lncRNA 在肿瘤中的作用和确切机制在很大程度上仍然未知。在本研究中,我们发现了一种新型长非编码 RNA,称为 SNAI3-AS1,其在 HCC 组织中的表达普遍高于正常对照。SNAI3-AS1 的高表达与 HCC 患者的总生存率显著相关。SNAI3-AS1 的敲低抑制了 HCC 细胞在体外的增殖和转移,而过表达 SNAI3-AS1 则促进了 HCC 细胞的增殖和转移。进一步的研究表明,SNAI3-AS1 可以通过结合上移框蛋白 1(UPF1)、调节 Smad7 表达和激活 TGF-β/Smad 通路来影响 HCC 肿瘤发生。功能上,SNAI3-AS1 通过诱导肿瘤上皮间质转化(EMT)促进 HCC 的生长和转移。总之,这些发现表明 SNAI3-AS1 通过调节 UPF1 和激活 TGF-β/Smad 通路促进 HCC 的进展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e7ca/6714236/04adbec192b1/JCMM-23-6271-g001.jpg

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