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长链非编码 RNA FENDRR 通过下调磷脂酰聚糖-3 的表达抑制肝癌的增殖和侵袭。

Long non-coding RNA FENDRR inhibits proliferation and invasion of hepatocellular carcinoma by down-regulating glypican-3 expression.

机构信息

Department of Liver Disease, Taizhou people's Hospital affiliated of Nantong University of medicine, Taizhou, China.

Department of Hepatobiliary Surgery, Taizhou people's Hospital affiliated of Nantong University of medicine, Taizhou, China.

出版信息

Biochem Biophys Res Commun. 2019 Jan 29;509(1):143-147. doi: 10.1016/j.bbrc.2018.12.091. Epub 2018 Dec 18.

Abstract

Long non-coding RNA FENDRR is implicated in progression of several cancers, but its exact role and mechanism in hepatocellular carcinoma (HCC) are largely unknown. In this study, we investigated the expression and biological roles of FENDRR in HCC tissues and cell lines. We found that the expression levels of FENDRR were significantly down-regulated in HCC tissues and cells. FENDRR overexpression could inhibit the growth of HCC cells in vitro and in vivo. Moreover, up-regulation of FENDRR suppressed the migration and invasion of HCC cells. Mechanistically, we demonstrated that FENDRR interacted directly with Glypican-3 (GPC3) promoter and methylated GPC3 promoter, which led to down-regulation of GPC3 expression. Ectopic expression of GPC3 ablated the inhibitory effects of FENDRR on HCC cell proliferation, migration and invasion. Taken together, we provided the first evidence for the inhibitory activity of FENDRR in HCC, which is causally linked to targeting GPC3 at the epigenetic level. Restoration of FENDRR may be a potential approach to prevent HCC progression and metastasis.

摘要

长链非编码 RNA FENDRR 参与了多种癌症的进展,但它在肝细胞癌 (HCC) 中的确切作用和机制在很大程度上尚不清楚。在本研究中,我们研究了 FENDRR 在 HCC 组织和细胞系中的表达和生物学作用。我们发现,FENDRR 的表达水平在 HCC 组织和细胞中明显下调。FENDRR 的过表达可以抑制 HCC 细胞在体外和体内的生长。此外,上调 FENDRR 抑制了 HCC 细胞的迁移和侵袭。从机制上讲,我们证明了 FENDRR 与 Glypican-3 (GPC3) 启动子直接相互作用,并使 GPC3 启动子甲基化,导致 GPC3 表达下调。GPC3 的异位表达消除了 FENDRR 对 HCC 细胞增殖、迁移和侵袭的抑制作用。总之,我们首次提供了 FENDRR 在 HCC 中具有抑制活性的证据,这与在表观遗传水平上靶向 GPC3 有关。恢复 FENDRR 可能是预防 HCC 进展和转移的一种潜在方法。

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