Long noncoding RNA BLACAT1 is overexpressed in hepatocellular carcinoma and its downregulation suppressed cancer cell development through endogenously competing against hsa-miR-485-5p

Biomed Pharmacother. 2019 Aug;116:109027. doi: 10.1016/j.biopha.2019.109027. Epub 2019 Jun 4.

Abstract

Objective: In this work, we explored the expression and mechanistic role of long noncoding RNA (lncRNA), bladder cancer associated transcript 1 (BLACAT1) in human hepatocellular carcinoma (HCC).

Methods: BLACAT1 expression in bothin vitro HCC cell lines and in vivo human HCC clinical samples were assessed by qRT-PCR. In HeG2 and MHCC97 L cells, BLACAT1 downregulation was induced by lentiviral infection to evaluate its functions in regulating HCC cancer cell proliferation and invasion in vitro, and xenograft in vivo. A BLACAT1 endogenously competing candidate, human microRNA-485-5p (has-miR-485-5p) was assessed in dual-luciferase assay and qRT-PCR in HCC cells. Furthermore, has-miR-485-5p was inhibited in BLACAT1-downregulated HeG2 and MHCC97 L cells to evaluate the correlation of has-miR-485-5p in BLACAT1-associated functional regulation in HCC cells.

Results: BLACAT1was found to be overexpressed in both HCC cells and human HCC tumors. In HeG2 and MHCC97 L cells, lentivirus-induced BLACAT1 downregulation inhibited cancer cellin vitro proliferation and invasion, and in vivo xenograft growth. Has-miR-485-5p was confirmed to be bound by BLACAT1 and its expression in HCC cells inversely regulated by BLACAT1. Then, has-miR-485-5p downregulation reversed the inhibitory effects of BLACAT1 downregulation on HCC cancer cell in vitro functions.

Conclusion: BLACAT1 is aberrantly upregulated in HCC and its inhibition had tumor suppressing effects in human HCC, possibly through endogenously competing against has-miR-485-5p. The BLACAT1/ has-miR-485-5p regulatory axis may be a molecular target for future HCC therapy.

Keywords: BLACAT; Hepatocellular carcinoma; has-miR-485-5p; lncRNA; miRNA.

MeSH terms

  • Animals
  • Base Sequence
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / pathology
  • Cell Proliferation / genetics
  • Down-Regulation / genetics*
  • Gene Expression Regulation, Neoplastic*
  • Hep G2 Cells
  • Humans
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / pathology
  • Male
  • Mice, Nude
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Neoplasm Invasiveness
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • Xenograft Model Antitumor Assays

Substances

  • MIRN485 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • long noncoding RNA BLACAT1, human