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

Dai W, Miao H, Fang S, Fang T, Chen N, Li M - Mol Med Rep (2016)

Bottom Line: The CDKN3 expression level was significantly decreased in HCC tumor tissues compared with normal liver tissue and liver cirrhosis tissue.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Hepatobiliary Surgery, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong 524001, P.R. China.

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.

No MeSH data available.


Related in: MedlinePlus

CDKN3 expression is downregulated in HCC tissues. (A) CDKN3 protein in normal liver, liver cirrhosis and HCC tissues was detected using immunohistochemistry. (B) CDKN3 expression content in the different tissues was evaluated. ***P<0.001, HCC vs. liver cirrhosis; ***P<0.001, HCC vs. normal liver. CDKN3, cyclin-dependent kinase inhibitor 3; HCC, hepatocellular carcinoma.
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f1-mmr-14-02-1509: CDKN3 expression is downregulated in HCC tissues. (A) CDKN3 protein in normal liver, liver cirrhosis and HCC tissues was detected using immunohistochemistry. (B) CDKN3 expression content in the different tissues was evaluated. ***P<0.001, HCC vs. liver cirrhosis; ***P<0.001, HCC vs. normal liver. CDKN3, cyclin-dependent kinase inhibitor 3; HCC, hepatocellular carcinoma.

Mentions: CDKN3 protein level in tissues was detected by IHC. A total of 70 HCC tissue, 10 liver tissue and 6 liver cirrhosis tissue samples were examined. The characteristics of the samples in each group are presented in Table I. Statistical analysis identified no significant difference in age and gender among the groups. Notably, the hepatitis B virus (HBV) infection ratio was significantly higher in HCC tissues compared with normal liver tissues (P=0.041). Additionally, CDKN3 expression levels were higher in normal and liver cirrhosis tissues compared with HCC tissues (Fig. 1; P=0.00034).


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

Dai W, Miao H, Fang S, Fang T, Chen N, Li M - Mol Med Rep (2016)

CDKN3 expression is downregulated in HCC tissues. (A) CDKN3 protein in normal liver, liver cirrhosis and HCC tissues was detected using immunohistochemistry. (B) CDKN3 expression content in the different tissues was evaluated. ***P<0.001, HCC vs. liver cirrhosis; ***P<0.001, HCC vs. normal liver. CDKN3, cyclin-dependent kinase inhibitor 3; HCC, hepatocellular carcinoma.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4940071&req=5

f1-mmr-14-02-1509: CDKN3 expression is downregulated in HCC tissues. (A) CDKN3 protein in normal liver, liver cirrhosis and HCC tissues was detected using immunohistochemistry. (B) CDKN3 expression content in the different tissues was evaluated. ***P<0.001, HCC vs. liver cirrhosis; ***P<0.001, HCC vs. normal liver. CDKN3, cyclin-dependent kinase inhibitor 3; HCC, hepatocellular carcinoma.
Mentions: CDKN3 protein level in tissues was detected by IHC. A total of 70 HCC tissue, 10 liver tissue and 6 liver cirrhosis tissue samples were examined. The characteristics of the samples in each group are presented in Table I. Statistical analysis identified no significant difference in age and gender among the groups. Notably, the hepatitis B virus (HBV) infection ratio was significantly higher in HCC tissues compared with normal liver tissues (P=0.041). Additionally, CDKN3 expression levels were higher in normal and liver cirrhosis tissues compared with HCC tissues (Fig. 1; P=0.00034).

Bottom Line: The CDKN3 expression level was significantly decreased in HCC tumor tissues compared with normal liver tissue and liver cirrhosis tissue.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Hepatobiliary Surgery, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong 524001, P.R. China.

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.

No MeSH data available.


Related in: MedlinePlus