CDKN3 expression predicates poor prognosis and regulates adriamycin sensitivity in hepatocellular carcinoma in vitro

J Int Med Res. 2020 Jul;48(7):300060520936879. doi: 10.1177/0300060520936879.

Abstract

Objective: Hepatocellular carcinoma (HCC) is one of the most common causes of cancer-related deaths worldwide. This study investigated the relationship between cyclin-dependent kinase inhibitor (CDKN)3 and prognosis and pathological characteristics in HCC patients to determine whether it could be used as a prognostic factor and/or therapeutic target for HCC drug development.

Methods: We previously showed that CDKN3 is deregulated in HCC tumor samples. Here, bioinformatics analysis was used to assess the relationship between CDKN3 gene expression and the characteristics of HCC patients from Gene Expression Omnibus and The Cancer Genome Atlas databases. Additionally, CDKN3 expression was silenced by small interfering RNA to determine its effect on HCC cell proliferation and on HCC cell sensitivity to adriamycin chemotherapy.

Results: Bioinformatics analysis showed a negative correlation between CDKN3 expression and both disease-free survival and overall survival. CDKN3 silencing did not significantly suppress the proliferation of HCC cells, but did decrease their sensitivity to adriamycin.

Conclusions: CDKN3 may have a dual role during the development of HCC, and could be used as an independent prognostic factor and therapeutic target for HCC treatment.

Keywords: Cyclin-dependent kinase inhibitor 3; Gene Expression Omnibus database; The Cancer Genome Atlas database; adriamycin; bioinformatics analysis; hepatocellular carcinoma.

MeSH terms

  • Carcinoma, Hepatocellular* / drug therapy
  • Carcinoma, Hepatocellular* / genetics
  • Cyclin-Dependent Kinase Inhibitor Proteins
  • Doxorubicin / pharmacology
  • Dual-Specificity Phosphatases
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Liver Neoplasms* / drug therapy
  • Liver Neoplasms* / genetics
  • Prognosis
  • RNA, Small Interfering / genetics

Substances

  • Cyclin-Dependent Kinase Inhibitor Proteins
  • RNA, Small Interfering
  • Doxorubicin
  • CDKN3 protein, human
  • Dual-Specificity Phosphatases