4.3 Article

TFAP2A-induced SLC2A1-AS1 promotes cancer cell proliferation

期刊

BIOLOGICAL CHEMISTRY
卷 402, 期 6, 页码 717-727

出版社

WALTER DE GRUYTER GMBH
DOI: 10.1515/hsz-2020-0290

关键词

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

资金

  1. Key Scientific Research Projects of Institutions of Higher Learning in Henan Province [20A310018]
  2. Joint Project for Medical Science and Technology of Henan Province [LHGJ20191054]

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The study revealed that lncRNA SLC2A1-AS1 is significantly over-expressed in lung adenocarcinoma (LUAD) and is closely correlated with patients' overall survival, acting as an oncogene to promote cancer cell proliferation. Additionally, the transcription factor TFAP2A can directly bind to the promoter region of SLC2A1-AS1 gene and positively regulate its transcription, further promoting cell proliferation in lung squamous cell carcinoma and pancreatic adenocarcinoma.
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 alpha (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.

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