SP1-induced upregulation of lncRNA CTBP1-AS2 accelerates the hepatocellular carcinoma tumorigenesis through targeting CEP55 via sponging miR-195-5p

Biochem Biophys Res Commun. 2020 Dec 17;533(4):779-785. doi: 10.1016/j.bbrc.2020.09.080. Epub 2020 Sep 26.

Abstract

As reported in many research, LncRNA CTBP1 divergent transcript (CTBP1-AS2) remarkably affects the progression of several tumors. However, the precise role and function of CTBP1-AS2 in hepatocellular carcinoma (HCC) remained unknown. We found that CTBP1-AS2 expressions were increased in HCC samples and cells. After treatment with microwave ablation (MWA), CTBP1-AS2 was distinctly up-regulated in residual HCC tissues compared with HCC samples. CTBP1-AS2 was upregulated under the induction of the nuclear transcription factor SP1. As revealed by the clinical assays, high CTBP1-AS2 expression usually related to lymph node metastasis, clinical stage and weaker prognosis specific to HCC patients. Functionally, CTBP1-AS2 knockdown suppressed HCC cells in terms of the proliferation, migration, invasion, chemotherapy resistance as well as EMT progress, but promoted apoptosis. Mechanistically, CTBP1-AS2 was a sponge of miR-195-5p for elevating CEP55 expression, a target of miR-195-5p, and thereby exhibited its oncogenic roles in HCC progression. Overall, an emerging regulatory mechanism of SP1/CTBP1-AS2/miR-195-5p/CEP55 axis was reported in the paper, which possibly served as a new therapeutic HCC treatment target.

Keywords: Biomarker; CEP55; CTBP1-AS2; Hepatocellular carcinoma; Metastasis; SP1; miR-195-5p.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis
  • Carcinogenesis / genetics
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / pathology
  • Cell Cycle Proteins / genetics*
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / pathology
  • MicroRNAs / metabolism*
  • Neoplasm Invasiveness
  • Prognosis
  • RNA, Long Noncoding / biosynthesis
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / physiology*
  • Sp1 Transcription Factor / metabolism*
  • Up-Regulation

Substances

  • Cell Cycle Proteins
  • Cep55 protein, human
  • MIRN195 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • Sp1 Transcription Factor
  • SP1 protein, human