Pseudogene PDIA3P1 promotes cell proliferation, migration and invasion, and suppresses apoptosis in hepatocellular carcinoma by regulating the p53 pathway

Cancer Lett. 2017 Oct 28:407:76-83. doi: 10.1016/j.canlet.2017.07.031. Epub 2017 Aug 18.

Abstract

Pseudogenes are a subclass of long non-coding (lnc) RNAs that arose from protein-coding genes, but have lost the ability to produce proteins. Pseudogenes play an important role in the pathogenesis of various tumors; however, the role of pseudogenes in hepatocellular carcinoma (HCC) is poorly understood. In this study, we investigated a novel pseudogene, PDIA3P1, which was upregulated in HCC tissues compared with paired normal adjacent tissues. The expression of PDIA3P1 was significantly correlated with tumor size, metastasis, TNM stage, and overall stage. Knockdown of PDIA3P1decreased proliferation, migration, and invasion of HCC cells. PDIA3P1 knockdown also promoted cell apoptosis and inhibited tumor growth in vivo. We performed a GeneChip assay to investigate the underlying mechanism of PDIA3P1 action on biological function, and our results suggested that PDIA3P1 may promote proliferation and inhibit apoptosis of liver cancer cells by inhibiting the p53 pathway. Thus, our data suggest that PDIA3P1 acts as an oncogene in HCC and could be a potential prognostic marker and therapeutic target for HCC.

Keywords: Hepatocellular carcinoma; Long noncoding RNA; Pseudogene; p53.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Animals
  • Apoptosis / physiology
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / mortality
  • Carcinoma, Hepatocellular / pathology
  • Cell Movement / physiology
  • Cell Proliferation / physiology
  • Disease Models, Animal
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunohistochemistry
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / mortality
  • Liver Neoplasms / pathology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Middle Aged
  • Neoplasm Invasiveness
  • Protein Disulfide-Isomerases / metabolism
  • Protein Disulfide-Isomerases / physiology*
  • RNA, Long Noncoding / physiology*
  • Survival Analysis
  • Tumor Cells, Cultured
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism*

Substances

  • RNA, Long Noncoding
  • Tumor Suppressor Protein p53
  • Protein Disulfide-Isomerases
  • PDIA3 protein, human