LncRNA PCAT6 predicts poor prognosis in hepatocellular carcinoma and promotes proliferation through the regulation of cell cycle arrest and apoptosis

Cell Biochem Funct. 2020 Oct;38(7):895-904. doi: 10.1002/cbf.3510. Epub 2020 Feb 16.

Abstract

Long noncoding RNAs have been proved in regulating tumourigenesis, including hepatocellular carcinoma (HCC). However, up to date, the role of PCAT6 in HCC is rare to be reported. In current study, bioinformatics analysis and quantitative real-time PCR were applied to examine the expression of PCAT6 in HCC. The role of PCAT6 in cell proliferation, cell cycle arrest, apoptosis, and metastasis were detected in both gain- and loss-of-function studies by cell biological assays. Bioinformatics analysis was employed to investigate the PCAT6-related genes and pathways in HCC. And we found that PCAT6 was significantly upregulated in HCC tissues and correlated with poor overall survival and disease-free survival in HCC patients. Furthermore, elevated PCAT6 promoted cell proliferation, inhibited cell cycle arrest and cell apoptosis while deficiency of PCAT6 impaired cell proliferation, caused cell cycle arrest and induced cell apoptosis of HCC. Moreover, as for bioinformatics analysis, a total of 389 PCAT6-related genes were found in both HCC tissue and cell lines, and these promising target genes were highly enriched in various key pathways, such as Wnt, HIF-1 signalling pathway, and metabolic pathways. Additionally, among these genes, DCAF13, SNRPB2, RPS8, and FKBP1A were revealed to be overexpressed in HCC and predicted poor prognosis. Taken together, our findings illustrate that PCAT6 contributes to HCC progression and might be a potential target for HCC therapy. Bioinformatics analysis may present a new way for assessing the underlying mechanism of PCAT6 in HCC. SIGNIFICANCE OF THE STUDY: Hepatocellular carcinoma (HCC) is one of the most common and malignant tumours all over the world. In this study, we observed that PCAT6 was upregulated in HCC and correlated with poor prognosis of HCC patients. PCAT6 could promote cell proliferation, inhibit cell cycle arrest and cell apoptosis of HCC, suggesting PCAT6 exerts tumorigenic role in HCC. Moreover, bioinformatics analysis revealed a total of 389 PCAT6-related genes in both HCC tissue and cell lines, and these promising target genes were highly enriched in various key pathways, such as Wnt, HIF-1 signalling pathway, and metabolic pathways. These finding provided evidence that PACT6 may be identified as a strategy to treat HCC in the future.

Keywords: LncRNAs; PCAT6; bioinformatics analysis; hepatocellular carcinoma; proliferation.

MeSH terms

  • Apoptosis*
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / mortality
  • Carcinoma, Hepatocellular / pathology*
  • Cell Cycle Checkpoints*
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Disease-Free Survival
  • Humans
  • Kaplan-Meier Estimate
  • Liver Neoplasms / genetics
  • Liver Neoplasms / mortality
  • Liver Neoplasms / pathology*
  • Prognosis
  • Protein Interaction Maps / genetics
  • RNA Interference
  • RNA, Long Noncoding / metabolism*
  • RNA, Small Interfering / metabolism
  • Up-Regulation

Substances

  • RNA, Long Noncoding
  • RNA, Small Interfering