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You Y.,Luohe Medical College | Yang W.,Ningxia Medical University | Wang Z.,Ningxia Medical University | Zhu H.,Third Affiliated Hospital of Luohe Medical College | And 3 more authors.
Cellular Oncology | Year: 2013

Background: Previous studies have shown a down-regulation of the gene encoding cyclin-dependent kinase 10 (CDK10) in hepatocellular carcinomas. Here we provide evidence that down-regulation of the CDK10 gene is mediated by promoter hypermethylation in primary human nasopharyngeal carcinomas (NPC) and NPC-derived cell lines. Methods: RT-PCR, Western blotting, methylation-specific PCR and bisulfite sequencing were performed to assess the expression and methylation status of the CDK10 gene in primary NPC samples, NPC-derived cell lines and patient-derived peripheral blood samples. The NPC-derived cell line CNE-2 was selected for treatment with a methylation inhibitor to restore CDK10 expression. In addition, cell proliferation, invasion and colony formation assays were performed to assess the inhibitory effects of ectopic CDK10 expression in CNE-2 cells. Results: Down-regulation of CDK10 expression in primary NPC samples (23/40, 57.5 %) was found to be significantly correlated with the methylation status of its promoter CpG island (21/40, 52.5 %). Demethylation by 5-aza-dC treatment led to reactivation of the CDK10 gene in the CNE-2 cell line. Additionally, exogenous expression of CDK10 in CNE-2 cells strongly suppressed its growth, invasion and colony formation capacities. The high sensitivity (15/40, 37.5 %) and specificity (0 % false positives) of detecting CDK10 promoter hypermethylation in NPC patient-derived peripheral blood samples suggest that it could be employed as an epigenetic marker for noninvasive cancer diagnosis and recurrence screening. Conclusion: Our findings implicate that aberrant methylation of the CDK10 gene promoter occurs frequently in NPC, and that reactivation of CDK10 might be utilized as a novel epigenetic strategy for the treatment of NPC patients. © 2013 International Society for Cellular Oncology. Source


You Y.,Luohe Medical College | You Y.,Luohe Key Laboratory of Medical Bioengineering | Yang W.,Ningxia Medical University | Qin X.,Hubei University of Arts and Science | And 8 more authors.
Cellular Oncology | Year: 2015

Background: Human nasopharyngeal carcinoma (NPC) is a malignant type of cancer with an increasing incidence. As yet, however, molecular biomarkers with a strong diagnostic impact and a major therapeutic promise have remained elusive. Here, we identified the esophageal carcinoma related gene 4 (ECRG4) as a novel candidate tumor suppressor gene and a promising therapeutic target for NPC. Methods: RT-PCR, Western blotting, methylation-specific PCR and bisulfite sequencing were performed to assess the expression and methylation status of the ECRG4 gene in primary NPC samples, NPC-derived cell lines and patient-derived peripheral blood samples. The NPC-derived cell line CNE1 was selected for treatment with a methylation inhibitor to restore ECRG4 expression. In addition, cell proliferation, invasion and colony formation assays were performed to assess the inhibitory effects of exogenous ECRG4 expression in CNE1 cells. Results: Down-regulated ECRG4 expression was found to occur in 82.5 % (33/40) of the primary NPC biopsies tested. This down-regulation was significantly correlated with its tumor-specific promoter methylation status (72.5 %, 29/40) and was also observed in the matching peripheral blood samples from the NPC patients (57.5 %, 23/40). Pharmacologic demethylation through 5-aza-dC treatment led to gene reactivation in ECRG4 methylated and silenced NPC cell lines. Moreover, exogenous expression of ECRG4 in the CNE1 cell line strongly inhibited its growth and invasive capacities, as well as its enhanced chemosensitivity to cisplatin through autophagy induction. Conclusion: Our data suggest that methylation-mediated suppression of the ECRG4 gene occurs frequently in NPC and that restoration of its expression may have therapeutic benefits. © 2015, International Society for Cellular Oncology. Source


You Y.,Pathological Examination and Research Center | You Y.,Luohe Medical College | You Y.,Luohe Key Laboratory of Medical Bioengineering | Li H.,The Second Peoples Hospital of Neijiang City | And 5 more authors.
Cellular Oncology | Year: 2015

Background: Cyclin-dependent kinase 10 (CDK10) has recently been identified as a tumor suppressor and, concordantly, its encoding gene has frequently been found to be inactivated in various human cancers. Here, we examined the expression status of CDK10 in a panel of primary human breast cancers and evaluated its correlation with clinicopathological parameters and clinical outcome. Methods: Western blotting was used to assess CDK10 protein levels in 20 paired breast cancer tissues and adjacent noncancerous tissues. In addition, immunohistochemistry was performed in 128 formalin-fixed, paraffin-embedded tumor tissues. Associations of CDK10 expression with various clinicopathological parameters were evaluated and Kaplan-Meier survival analyses and Cox proportional hazards models were used to estimate its effect on patient survival. Results: We found that CDK10 protein expression was markedly decreased in cancer tissues compared to adjacent noncancerous tissues. Immunohistochemistry revealed decreased CDK10 levels in 65/128 (50.8 %) of the primary breast cancer tissues tested. These decreased levels were found to be significantly associated with lymph node metastasis (P = 0.003), advanced tumor stage (P < 0.001) and unfavorable overall survival (P < 0.001). Furthermore, multivariate analyses indicated that CDK10 expression may serve as an independent prognostic factor for survival (P = 0.001). Conclusion: Down-regulated CDK10 expression frequently occurs in breast cancers and correlates with disease progression and poor survival. CDK10 may serve as a prognostic biomarker for breast cancer. © 2015, International Society for Cellular Oncology. Source


You Y.,Pathological Examination and Research Center | You Y.,Luohe Medical College | Li H.,The Second Peoples Hospital of Neijiang City | Qin X.,Hubei University of Arts and Science | And 2 more authors.
Cellular Oncology | Year: 2016

Background: Recently, we identified the esophageal carcinoma related gene 4 (ECRG4) as a novel candidate tumor suppressor gene and a promising therapeutic target in nasopharyngeal carcinoma (NPC). In addition, we found that reduced ECRG4 expression in NPC was associated with promoter hypermethylation. The aim of the current study was to assess the expression status of the ECRG4 protein in breast cancer and to clarify its clinicopathological significance and potential prognostic implications. Methods: Western blotting was used to examine ECRG4 protein levels in 20 paired breast cancer tissues and adjacent noncancerous tissues. In addition, we performed ECRG4 immunohistochemistry on 113 clinicopathologically well-characterized breast cancer samples and assessed putative associations between its expression and overall patient survival rates. Results: We found that ECRG4 protein expression was significantly reduced in the breast cancer tissues compared to the noncancerous tissues. Clinicopathological analyses revealed that loss of ECRG4 protein expression, observed in 41.6 % (47/113) of the primary breast cancer tissues tested, was significantly correlated with lymph node metastasis (P = 0.026), advanced tumor stage (P = 0.042) and unfavorable overall survival (P = 0.004). Additional multivariate analyses revealed that ECRG4 protein expression may serve as an independent prognostic factor for the prediction of patient survival (P = 0.033). Conclusion: Our data suggest that loss of ECRG4 protein expression may be involved in tumor progression and may serve as a prognostic biomarker for breast cancer. © 2015, International Society for Cellular Oncology. Source

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