School of Life Sciences, Zhengzhou University, Zhengzhou450001, China.
Department of Clinical Laboratory, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou450007, China.
Biol Chem. 2021 Feb 19;402(6):717-727. doi: 10.1515/hsz-2020-0290. Print 2021 May 26.
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.
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。