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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

Depletion of CDKN3 increased cell survival and cisplatin tolerance by activation of the AKT/p53/p21 pathway. (A) Tumor clone formation assay was performed to test clone formation capacity of different tumor cells. (B) Clone formation assay data. ***P<0.001, comparison indicated by brackets. Cell viability of cells was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay following (C) 48 h and (D) 72 h cisplatin treatment. *P<0.05 vs. the scramble control. (E) Western blotting was used to detect the levels of the AKT/p53/p21 signaling pathway proteins. siRNA, small interfering RNA; CDKN3, cyclin-dependent kinase inhibitor 3; AKT, AKT serine/threonine kinase 1; OD, optical density.
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f3-mmr-14-02-1509: Depletion of CDKN3 increased cell survival and cisplatin tolerance by activation of the AKT/p53/p21 pathway. (A) Tumor clone formation assay was performed to test clone formation capacity of different tumor cells. (B) Clone formation assay data. ***P<0.001, comparison indicated by brackets. Cell viability of cells was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay following (C) 48 h and (D) 72 h cisplatin treatment. *P<0.05 vs. the scramble control. (E) Western blotting was used to detect the levels of the AKT/p53/p21 signaling pathway proteins. siRNA, small interfering RNA; CDKN3, cyclin-dependent kinase inhibitor 3; AKT, AKT serine/threonine kinase 1; OD, optical density.

Mentions: To determinate the function of CDKN3 in QGY7701 cells, CDKN3 was knocked-down by transfection with CDKN3-specific siRNA. The knockdown of CDKN3 enhanced the colony formation capacity of the cells at 12 h. Larger tumor cell colonies formed following CDKN3 knockdown compared with the control group, in addition, the number of colonies also increased compared with the control group (Fig. 3A and B). Cisplatin is frequently used for the treatment of cancer. Thus, QGY7701 cells were treated with cisplatin following CDKN3 knockdown and cell viability was measured. QGY7701-KD cells exhibited a higher tolerance to cisplatin compared with the control group (P=0.024; Fig. 3C and D).


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)

Depletion of CDKN3 increased cell survival and cisplatin tolerance by activation of the AKT/p53/p21 pathway. (A) Tumor clone formation assay was performed to test clone formation capacity of different tumor cells. (B) Clone formation assay data. ***P<0.001, comparison indicated by brackets. Cell viability of cells was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay following (C) 48 h and (D) 72 h cisplatin treatment. *P<0.05 vs. the scramble control. (E) Western blotting was used to detect the levels of the AKT/p53/p21 signaling pathway proteins. siRNA, small interfering RNA; CDKN3, cyclin-dependent kinase inhibitor 3; AKT, AKT serine/threonine kinase 1; OD, optical density.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f3-mmr-14-02-1509: Depletion of CDKN3 increased cell survival and cisplatin tolerance by activation of the AKT/p53/p21 pathway. (A) Tumor clone formation assay was performed to test clone formation capacity of different tumor cells. (B) Clone formation assay data. ***P<0.001, comparison indicated by brackets. Cell viability of cells was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay following (C) 48 h and (D) 72 h cisplatin treatment. *P<0.05 vs. the scramble control. (E) Western blotting was used to detect the levels of the AKT/p53/p21 signaling pathway proteins. siRNA, small interfering RNA; CDKN3, cyclin-dependent kinase inhibitor 3; AKT, AKT serine/threonine kinase 1; OD, optical density.
Mentions: To determinate the function of CDKN3 in QGY7701 cells, CDKN3 was knocked-down by transfection with CDKN3-specific siRNA. The knockdown of CDKN3 enhanced the colony formation capacity of the cells at 12 h. Larger tumor cell colonies formed following CDKN3 knockdown compared with the control group, in addition, the number of colonies also increased compared with the control group (Fig. 3A and B). Cisplatin is frequently used for the treatment of cancer. Thus, QGY7701 cells were treated with cisplatin following CDKN3 knockdown and cell viability was measured. QGY7701-KD cells exhibited a higher tolerance to cisplatin compared with the control group (P=0.024; Fig. 3C and D).

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