TFAP2A-induced SLC2A1-AS1 promotes cancer cell proliferation

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 in vitro, 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.

Keywords: LUAD; SLC2A1-AS1; TFAP2A; cancer cell proliferation; miR-508-5p.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma of Lung / metabolism*
  • Adenocarcinoma of Lung / pathology
  • Apoptosis
  • Cell Proliferation
  • Cells, Cultured
  • Computational Biology
  • Humans
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / pathology
  • MicroRNAs / genetics
  • MicroRNAs / metabolism
  • Pancreatic Neoplasms / metabolism*
  • Pancreatic Neoplasms / pathology
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • Transcription Factor AP-2 / genetics
  • Transcription Factor AP-2 / metabolism*

Substances

  • MIRN508 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • TFAP2A protein, human
  • Transcription Factor AP-2