LncRNA CRNDE promotes hepatocellular carcinoma cell proliferation, invasion, and migration through regulating miR-203/ BCAT1 axis

J Cell Physiol. 2019 May;234(5):6548-6560. doi: 10.1002/jcp.27396. Epub 2018 Sep 19.

Abstract

Objective: To investigate the impact of long noncodingRNA (lncRNA) colorectal neoplasia differentially expressed (CRNDE) on hepatocellular cancer (HCC) cell propagation, invasion, and migration by mediating miR-203/ BCAT1 axis.

Methods: Microarray analysis was based on 25 pairs of HCC cancerous tissues and adjacent tissues. The expression levels of CRNDE, miR-203, and BCAT1 in HCC tissues were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR). The liver cell line L-02 and HCC cell lines HepG2 and Huh-7 were utilized to assess the regulatory effects of CRNDE and miR-203 on HCC progression in vitro. Western blot was used to qualify BCAT1 protein expression level. Cell proliferation and apoptosis were evaluated using CCK-8 and flow cytometry analysis, whereas cell invasion and migration assay were performed by the Transwell assay. The relationship among CRNDE, miR-203, and BCAT1 was validated by dual luciferase assay. Tumor Xenograft study was established to verify the pathological effect of CRNDE on HCC development in vivo.

Results: The expression levels of the CRNDE and BCAT1 were upregulated in HCC tissues and cells, whereas miR-203 was downregulated in HCC. Knockdown of CRNDE or miR-203 overexpression would inhibit HCC cell propagation and metastasis, and induced cell apoptosis. Moreover, miR-203 was negatively correlated with CRNDE, the same as miR-203 with BCAT1. Dual luciferase assay showed that miR-203 was an inhibitory target of CRNDE, and BCAT1 was directly targeted by miR-203 as well.

Conclusion: LncRNA CRNDE could enhance HCC tumorgenesis by sponging miR-203 and mediating BCAT1. LncRNA CRNDE might facilitate HCC cell propagation, invasiveness, and migration through regulating miR-203/ BCAT1 axis.

Keywords: BCAT1; CRNDE; hepatocellular carcinoma cell; miR-203; proliferation.

Publication types

  • Retracted Publication

MeSH terms

  • Carcinoma, Hepatocellular / genetics*
  • Cell Line, Tumor
  • Cell Movement / genetics*
  • Cell Proliferation / genetics
  • Colorectal Neoplasms / genetics
  • Disease Progression
  • Gene Expression Regulation, Neoplastic / genetics
  • Hep G2 Cells
  • Humans
  • Liver Neoplasms / genetics
  • Liver Neoplasms / pathology
  • MicroRNAs / genetics*
  • RNA, Long Noncoding / genetics*

Substances

  • MIRN203 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • long non-coding RNA BCAT1, human