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TFAP2A 诱导的 SLC2A1-AS1 促进癌细胞增殖。

TFAP2A-induced SLC2A1-AS1 promotes cancer cell proliferation.

机构信息

School of Life Sciences, Zhengzhou University, Zhengzhou450001, China.

Department of Clinical Laboratory, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou450007, China.

出版信息

Biol Chem. 2021 Feb 19;402(6):717-727. doi: 10.1515/hsz-2020-0290. Print 2021 May 26.

Abstract

Long non-coding RNAs (lncRNAs) are involved in the occurrence and development of human cancers including lung adenocarcinoma (LUAD). SLC2A1-AS1 is a novel lncRNA that has been reported to be exceptionally expressed in several cancer types. However, the expression and role of SLC2A1-AS1 in cancer remains largely unclear. In this study, it was revealed that lncRNA SLC2A1-AS1 was notably over-expressed in LUAD and was closely correlated with patients' overall survival (OS). Knockdown of SLC2A1-AS1 could significantly restrain cell proliferation of LUAD , while over-expression of SLC2A1-AS1 had the accelerative effect. SLC2A1-AS1 enriched in the cytoplasm of LUAD cells could directly bind to miR-508-5p and negatively regulate its level. The inhibitory effect of miR-508-5p on LUAD cell proliferation was in part abrogated by SLC2A1-AS1 manipulation. Moreover, the transcription factor activating enhancer binding protein 2 α (TFAP2A) was highly expressed in LUAD and predicted worse patients' OS. TFAP2A could directly bind to the promoter region of SLC2A1-AS1 encoding gene and positively regulate the transcription of SLC2A1-AS1 in LUAD cells. Furthermore, TFAP2A-induced SLC2A1-AS1 promoted cell proliferation of lung squamous cell carcinoma (LUSC) and pancreatic adenocarcinoma (PAAD). Collectively, these findings suggest that TFAP2A-mediated lncRNA SLC2A1-AS1 works as an oncogene to drive cancer cell proliferation.

摘要

长链非编码 RNA(lncRNAs)参与包括肺腺癌(LUAD)在内的人类癌症的发生和发展。SLC2A1-AS1 是一种新型的 lncRNA,已被报道在几种癌症类型中异常表达。然而,SLC2A1-AS1 在癌症中的表达和作用在很大程度上仍不清楚。在这项研究中,发现 lncRNA SLC2A1-AS1 在 LUAD 中显著过表达,并且与患者的总生存期(OS)密切相关。SLC2A1-AS1 的敲低显著抑制 LUAD 细胞的增殖,而过表达 SLC2A1-AS1 则具有加速作用。SLC2A1-AS1 在 LUAD 细胞的细胞质中富集,可直接与 miR-508-5p 结合并负调控其水平。SLC2A1-AS1 操纵部分消除了 miR-508-5p 对 LUAD 细胞增殖的抑制作用。此外,转录因子激活增强子结合蛋白 2α(TFAP2A)在 LUAD 中高表达,并预测患者的 OS 更差。TFAP2A 可直接结合 SLC2A1-AS1 编码基因的启动子区域,并在 LUAD 细胞中正向调节 SLC2A1-AS1 的转录。此外,TFAP2A 诱导的 SLC2A1-AS1 促进肺鳞状细胞癌(LUSC)和胰腺腺癌(PAAD)的细胞增殖。总之,这些发现表明,TFAP2A 介导的 lncRNA SLC2A1-AS1 作为癌基因发挥作用,驱动癌细胞增殖。

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