Long Noncoding RNA GATA3-AS1 Promotes Cell Proliferation and Metastasis in Hepatocellular Carcinoma by Suppression of PTEN, CDKN1A, and TP53

Can J Gastroenterol Hepatol. 2019 Dec 2:2019:1389653. doi: 10.1155/2019/1389653. eCollection 2019.

Abstract

Background: Long noncoding RNAs (lncRNAs) have been known to play important roles in the progression of various types of human cancer. LncRNA GATA3 antisense RNA 1, GATA3-AS1, has been reported to be associated with T-cell development and differentiation. However, the expression pattern and function of GATA3-AS1 in hepatocellular carcinoma (HCC) remain unknown.

Methods: Real-time quantitative PCR (RT-qPCR) assay was conducted to detect GATA3-AS1 expression levels in 80 cases of pairs HCC tissues and matched normal tissues. Chi-squared (χ 2) test was used to analyze the correlation between GATA3-AS1 expression and clinicopathologic variables. Survival curves were plotted using the Kaplan-Meier method and were compared via the log-rank test. The cell counting kit-8 (CCK-8) and wound scratch assays were applied to detect the effect of GATA3-AS1 knockdown and overexpression on cell growth and migration of HCC. RT-qPCR was performed for the detection of the phosphatase and tensin homolog (PTEN), cyclin-dependent kinase inhibitor 1A (CDKN1A), and tumor protein p53 (TP53) expression in HCC cells after GATA3-AS1 knockdown and overexpression.

Results: GATA3-AS1 was significantly upregulated in HCC tissues compared with matched normal tissues. The high expression of GATA3-AS1 was significantly correlated with larger tumor size, advanced TNM stage, and more lymph node metastasis. High GATA3-AS1 expression was markedly correlated with shorter overall survival times of HCC patients. Furthermore, knockdown of GATA3-AS1 obviously inhibited Hep3B and HCCLM3 cell growth and migration, whereas overexpression of GATA3-AS1 had the opposite effects. In addition, GATA3-AS1 knockdown resulted in upregulated expression levels of tumor-suppressive genes, PTEN, CDKN1A, and TP53, in Hep3B and HCCLM3 cells, while restoration of GATA3-AS1 decreased PTEN, CDKN1A, and TP53 expression levels.

Conclusion: Our data suggested that GATA3-AS1 promotes cell proliferation and metastasis of HCC by suppression of PTEN, CDKN1A, and TP53.

MeSH terms

  • Carcinoma, Hepatocellular / genetics*
  • Cell Proliferation / genetics*
  • Cyclin-Dependent Kinase Inhibitor p21 / metabolism
  • Female
  • GATA3 Transcription Factor / physiology*
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • Liver Neoplasms / genetics*
  • Male
  • Middle Aged
  • Neoplasm Metastasis / genetics
  • PTEN Phosphohydrolase / metabolism
  • RNA, Antisense / physiology*
  • RNA, Long Noncoding / physiology*
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • CDKN1A protein, human
  • Cyclin-Dependent Kinase Inhibitor p21
  • GATA3 Transcription Factor
  • GATA3 protein, human
  • RNA, Antisense
  • RNA, Long Noncoding
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • PTEN Phosphohydrolase
  • PTEN protein, human