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长链非编码 RNA ELFN1-AS1 通过海绵吸附 miR-183-3p 而上调 GFPT1 促进食管癌进展。

LncRNA ELFN1-AS1 promotes esophageal cancer progression by up-regulating GFPT1 via sponging miR-183-3p.

机构信息

Department of Clinical Laboratory, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, 450007, China.

Department of Orthopedics, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, 450007, China.

出版信息

Biol Chem. 2020 Aug 27;401(9):1053-1061. doi: 10.1515/hsz-2019-0430.

Abstract

Accumulating studies highlight the critical role of long non-coding RNAs (lncRNAs) in the development of various human cancers. Extracellular leucine rich repeat and fibronectin type III domain containing 1-antisense RNA 1 (ELFN1-AS1) was shown to be a newly found lncRNA that abnormally expressed in human tumors. However, till now the specific function of this lncRNA in esophageal cancer (ESCA) remains unknown. In this study, we discovered that higher ELFN1-AS1 expression indicated shorter patient survival in pan-cancer, including ESCA, using online The Cancer Genome Atlas (TCGA) tools. The lncRNA ELFN1-AS1 was significantly up-regulated in ESCA tissues and cell lines when compared with the counterparts. Down-regulation of ELFN1-AS1 restrained cell proliferation, migration, and invasion of ESCA in vitro. In addition, we found that the expression of microRNA-183-3p (miR-183-3p) and ELFN1-AS1 or glutamine-fructose-6-phosphate transaminase 1 (GFPT1) were inversely correlated in ESCA. Both ELFN1-AS1 and GFPT1 are direct targets of miR-183-3p in ESCA. The effects of ELFN1-AS1 knockdown on ESCA progression were partially rescued by inhibition of miR-183-3p or over-expression of GFPT1. In summary, the results of this study suggest that the lncRNA ELFN1-AS1 facilitates the progression of ESCA by acting as a competing endogenous RNA (ceRNA) to promote GFPT1 expression via sponging miR-183-3p.

摘要

越来越多的研究强调长非编码 RNA(lncRNA)在各种人类癌症发展中的关键作用。细胞外亮氨酸丰富重复和纤维连接蛋白 III 结构域包含 1 反义 RNA 1(ELFN1-AS1)被证明是一种新发现的在人类肿瘤中异常表达的 lncRNA。然而,到目前为止,这种 lncRNA 在食管癌(ESCA)中的具体功能仍然未知。在这项研究中,我们使用在线癌症基因组图谱(TCGA)工具发现,ELFN1-AS1 表达水平较高的患者在泛癌(包括 ESCA)中的生存时间较短。与对照相比,ELFN1-AS1 在 ESCA 组织和细胞系中明显上调。下调 ELFN1-AS1 可抑制 ESCA 细胞体外增殖、迁移和侵袭。此外,我们发现 miR-183-3p(miR-183-3p)和 ELFN1-AS1 或谷氨酰胺果糖-6-磷酸转氨酶 1(GFPT1)在 ESCA 中的表达呈负相关。ELFN1-AS1 和 GFPT1 都是 miR-183-3p 在 ESCA 中的直接靶标。抑制 miR-183-3p 或过表达 GFPT1 可部分挽救 ELFN1-AS1 敲低对 ESCA 进展的影响。总之,这项研究的结果表明,lncRNA ELFN1-AS1 通过作为竞争性内源性 RNA(ceRNA)来促进 GFPT1 表达,从而促进 ESCA 的进展,通过海绵吸附 miR-183-3p。

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