CDKN3 expression is negatively associated with pathological tumor stage and CDKN3 inhibition promotes cell survival in hepatocellular carcinoma

Dai,Wei; Miao,Huilai; Fang,Shuo; Fang,Tao; Chen,Nianping; Li,Mingyi

doi:10.3892/mmr.2016.5410

CDKN3 expression is negatively associated with pathological tumor stage and CDKN3 inhibition promotes cell survival in hepatocellular carcinoma

Authors:
- Wei Dai
- Huilai Miao
- Shuo Fang
- Tao Fang
- Nianping Chen
- Mingyi Li
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Affiliations: Department of Hepatobiliary Surgery, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong 524001, P.R. China, Department of Endocrinology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong 524001, P.R. China
Published online on: June 17, 2016 https://doi.org/10.3892/mmr.2016.5410
Pages: 1509-1514
Copyright: © Dai et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Aberrant expression of CDKN3 may be involved in carcinogenesis of liver cancer. The effect of CDKN3 on tumorigenesis and the molecular mechanisms involved have not been fully elucidated. Immunohistochemistry was performed to detect CDKN3 expression levels in tumor tissues. CDKN3 siRNA was used to knockdown CDKN3 in QGY7701 hepatocellular carcinoma (HCC) cells. Colony formation assay was used to measure the clonogenic capacity of the tumor cells. Cell viability was determined by MTT assay. Logistic regression was performed to analyze the association between CDKN3 expression level and the HCC clinical pathology index. The CDKN3 expression level was significantly decreased in HCC tumor tissues compared with normal liver tissue and liver cirrhosis tissue. Additionally, CDKN3 expression was negatively‑associated with the pathological stage of the tumor. Inhibition of CKDN3 promoted the clonogenic capacity and chemotherapeutic tolerance in HCC tissues compared with controls. Knockdown of CDKN3 resulted in downregulation of p53 and p21 protein levels, whereas, AKT serine/threonine kinase 1 expression was upregulated. Thus, CDKN3 expression may reduce the survival of tumor cells and alter the sensitivity to therapeutic agents via the AKT/P53/P21 signaling pathway. Therefore, CDKN3 may be involved in tumor differentiation and self-renewal.

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