Overexpressed lncRNA CDKN2B-AS1 is an independent prognostic factor for liver cancer and promotes its proliferation

J BUON. 2019 Jul-Aug;24(4):1441-1448.

Abstract

Purpose: To study the expression of long non-coding RNA (lncRNA) CDKN2B-AS1 in the liver tissue of patients with liver cancer and its effect on the proliferation of liver cancer cell line QGY-7703.

Methods: The expression of differentially expressed genes in liver cancer tissues and normal liver tissues was analyzed by bioinformatics. The expressions of differentially expressed genes in clinical samples were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) to analyze whether there is a significant difference of CDKN2B-AS1 expression in clinical features of patients with liver cancer. The clinical data were analyzed to find out the correlation between the expressions of differentially expressed genes and the overall survival, tumor size and TNM staging. The Gene Set Enrichment Analysis (GSEA) enrichment analysis was used to predict the function of CDKN2B-AS1. The cell proliferation was measured by cell counting kit-8 (CCK-8) assay. Cell cycle was measured by flow cytometry. Expressions of proteins were detected by Western blotting.

Results: The expression of CDKN2B-AS1 in liver cancer was significantly higher compared to normal tissues. The results of qRT-PCR were consistent with the results of the Cancer Genome Atlas (TGCA). The data of CDKN2B-AS1 showed that the expression of CDKN2B-AS1 was associated with the total survival, tumor size and TNM staging. GSEA results showed that genes are enriched in cell cycle sets and others. Compared with the control, the proliferation of QGY-7703 cells overexpressing CDKN2B-AS1 was significantly increased (p<0.001). Western blotting results showed that the expressions of CDK2 and CDK4 were up-regulated and the expression of P16 was decreased after CDKN2B-AS1 was overexpressed.

Conclusions: LncRNA CDKN2B-AS1 was highly expressed in liver cancer, and its expression was positively correlated with the overall survival, tumor size and TNM stage. LncRNA CDKN2B-AS1 promoted the proliferation and expression of liver cancer cells.

MeSH terms

  • Aged
  • Biomarkers, Tumor / genetics
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / pathology
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Cyclin-Dependent Kinase 2 / genetics
  • Cyclin-Dependent Kinase 4 / genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / pathology
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Prognosis*
  • RNA, Long Noncoding / genetics*

Substances

  • Biomarkers, Tumor
  • CDKN2B antisense RNA, human
  • RNA, Long Noncoding
  • Cyclin-Dependent Kinase 2
  • Cyclin-Dependent Kinase 4