| 15090801 | CDKN3 expression is negatively associated with pathological tumor stage and CDKN3 inhibition promotes cell survival in hepatocellular carcinoma. | Dai W, etal., Mol Med Rep. 2016 Aug;14(2):1509-14. doi: 10.3892/mmr.2016.5410. Epub 2016 Jun 17. | 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. | 27314282 | 2016-08-01 |
| 11086809 | CDKN3 mRNA as a Biomarker for Survival and Therapeutic Target in Cervical Cancer. | Barron EV, etal., PLoS One. 2015 Sep 15;10(9):e0137397. doi: 10.1371/journal.pone.0137397. eCollection 2015. | The cyclin-dependent kinase inhibitor 3 (CDKN3) gene, involved in mitosis, is upregulated in cervical cancer (CC). We investigated CDKN3 mRNA as a survival biomarker and potential therapeutic target for CC. CDKN3 -weight:700;'>CDKN3 mRNA was measured in 134 CC and 25 controls by quantitative PCR. A 5-year survival study was conducted in 121 of these CC patients. Furthermore, CDKN3-specific siRNAs were used to investigate whether CDKN3 is involved in proliferation, migration, and invasion in CC-derived cell lines (SiHa, CaSki, HeLa). CDKN3 mRNA was on average 6.4-fold higher in tumors than in controls (p = 8 x 10-6, Mann-Whitney). A total of 68.2% of CC patients over expressing CDKN3 gene (fold change >/= 17) died within two years of diagnosis, independent of the clinical stage and HPV type (Hazard Ratio = 5.0, 95% CI: 2.5-10, p = 3.3 x 10-6, Cox proportional-hazards regression). In contrast, only 19.2% of the patients with lower CDKN3 expression died in the same period. In vitro inactivation of CDKN3 decreased cell proliferation on average 67%, although it had no effect on cell migration and invasion. CDKN3 mRNA may be a good survival biomarker and potential therapeutic target in CC. | 26372210 | 1000-06-01 |
| 11079602 | Overexpression of major CDKN3 transcripts is associated with poor survival in lung adenocarcinoma. | Fan C, etal., Br J Cancer. 2015 Dec 22;113(12):1735-43. doi: 10.1038/bjc.2015.378. Epub 2015 Nov 10. | BACKGROUND: The cyclin-dependent kinase inhibitor 3 (CDKN3) has been perceived as a tumour suppressor. Paradoxically, CDKN3 is often overexpressed in human cancer. It was unclear if CDKN3 > overexpression is linked to alternative splicing variants or mutations that produce dominant-negative CDKN3. METHODS: We analysed CDKN3 expression and its association with patient survival in three cohorts of lung adenocarcinoma. We also examined CDKN3 mutations in the Cancer Genome Atlas (TCGA) and the Moffitt Cancer Center's Total Cancer Care (TCC) projects. CDKN3 transcripts were further analysed in a panel of cell lines and lung adenocarcinoma tissues. CDKN3 mRNA and protein levels in different cell cycle phases were examined. RESULTS: CDKN3 is overexpressed in non small cell lung cancer. High CDKN3 expression is associated with poor overall survival in lung adenocarcinoma. Two CDKN3 transcripts were detected in all samples. These CDKN3 transcripts represent the full length CDKN3 mRNA and a normal transcript lacking exon 2, which encodes an out of frame 23-amino acid peptide with little homology to CDKN3. CDKN3 mutations were found to be very rare. CDKN3 mRNA and protein were elevated during the mitosis phase of cell cycle. CONCLUSIONS: CDKN3 overexpression is prognostic of poor overall survival in lung adenocarcinoma. CDKN3 overexpression in lung adenocarcinoma is not attributed to alternative splicing or mutation but is likely due to increased mitotic activity, arguing against CDKN3 as a tumour suppressor. | 26554648 | 2015-05-01 |
| 11073498 | CDKN3 knockdown reduces cell proliferation, invasion and promotes apoptosis in human ovarian cancer. | Zhang LP, etal., Int J Clin Exp Pathol. 2015 May 1;8(5):4535-44. eCollection 2015. | Cyclin-dependent kinase inhibitor 3 (CDKN3) has been reported to promote tumor genesis. The aim of this study is to investigate the possible mechanisms of silence of CDKN3 exerting the suppressive role on epithelial ovarian cancer (EOC). To study the potential function of CDKN3 enrolled in the regulation of ovarian tumor, we monitored the EOC cells SKOV3 and HO8910 behaviors including proliferation, cell cycle, apoptosis and invasion. First, we found that CDKN3 was frequently over-expressed in EOC. Functional studies showed that silence of CDKN3 inhibited cancer cell proliferation by promoting cell cycle progression in G1 phase, decreased cell invasion and promoted EOC cells apoptosis. Western blot analysis of CDKN3-silence cells revealed down-regulation of DNA-replication and cell cycle related proteins. And, a significant correlation level of CDKN3 was observed which has been demonstrated to be a novel oncogene. These findings indicated that CDKN3 might serve as a useful potential target for treatment of ovarian cancer. | 26191143 | 1000-04-01 |
| 728374 | Chromosomal mapping of the genes for the human cell cycle proteins cyclin C (CCNC), cyclin E (CCNE), p21 (CDKN1) and KAP (CDKN3). | Demetrick DJ, etal., Cytogenet Cell Genet 1995;69(3-4):190-2. | Many gene products associated with the cdk cell cycle kinases are thought to regulate the active kinase complex and thus regulate the transition points of the cell cycle. Genes encoding these proteins may potentially function as oncogenes or tumor suppressor genes. We describe the chromosomal mappin g by FISH of the genes for several cdk-associated proteins including human CCNC (cyclin C) to 6q21, CCNE (cyclin E) to 19q12-->q13, CDKN1 (p21) to 6p21.2 and CDKN3 (KAP to 14q22). Some of these sites are near chromosomal translocations or LOH sites common to a variety of human tumors. The potential role for each of these genes in neoplasia is discussed. | 7698009 | 1995-11-01 |
| 11534393 | The Tumor Suppressor Cdkn3 Is Required for Maintaining the Proper Number of Centrosomes by Regulating the Centrosomal Stability of Mps1. | Srinivas V, etal., Cell Rep. 2015 Nov 24;13(8):1569-77. doi: 10.1016/j.celrep.2015.10.039. Epub 2015 Nov 12. | Supernumerary centrosomes promote the assembly of abnormal spindles in many human cancers. The observation that modest changes in the centrosomal levels of Mps1 kinase can cause centrosome overduplication in human cells suggests the existence of a regulatory system that may tightly control its centr osomal stability. Here, we show that Cdkn3, a Cdk-associated phosphatase, prevents Mps1-mediated centrosome overduplication. We identify Cdkn3 as a direct binding partner of Mps1. The interaction between Mps1 and Cdkn3 is required for Mps1 to recruit Cdkn3 to centrosomes. Subsequently, Mps1-bound Cdkn3 forms a regulatory system that controls the centrosomal levels of Mps1 through proteasome-mediated degradation and thereby prevents Mps1-mediated centrosome overduplication. Conversely, knockdown of Cdkn3 stabilizes Mps1 at centrosomes, which promotes centrosome overduplication. We suggest that Mps1 and Cdkn3 form a self-regulated feedback loop at centrosomes to tightly control the centrosomal levels of Mps1, which prevents centrosome overduplication in human cells. | 26586430 | 2015-09-01 |
