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Jianbin Chen - One of the best experts on this subject based on the ideXlab platform.
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PCDH10 inhibits cell proliferation of multiple myeloma via the negative regulation of the wnt β catenin bcl 9 signaling pathway
Oncology Reports, 2015Co-Authors: Zesong Yang, Haiting Yuan, Qiong Liu, Jianbin ChenAbstract:The tumor suppressor protocadherin-10 (PCDH10) gene is important in cell proliferation, survival, apoptosis and migration. Inactivation of PCDH10 by promoter methylation is a frequent pathogenetic event in multiple myeloma (MM). The Wnt/β-catenin pathway is known to be involved in the cell growth of various types of cancer, including MM. However, the relationship between PCDH10 and Wnt signaling in MM remains unclear. In this study, we found that PCDH10 deficiency highly enhanced MM cell proliferation, Wnt signaling and the expression of BCL-9, an essential coactivator of Wnt transcriptional activity that is correlated with cell growth, survival and drug resistance. Restoration of PCDH10 suppressed nuclear localization of β-catenin, the activity of LEF/TCF, the expression of BCL-9 and AKT, whereas the expression of GSK3β was increased. The antagonistic effect of PCDH10 was associated with G1-phase blockage. Collectively, PCDH10 antagonized MM cell proliferation via the downregulation of Wnt/β-catenin/BCL-9 signaling, whereas PCDH10 repressed the expression of AKT to promote the expression of GSK3β and then to restrain the activation of β-catenin. Thus, the results offer a novel preclinical rationale in order to explore PCDH10 as an effective and selective therapeutic strategy to eradicate MM cells.
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PCDH10 inhibits cell proliferation of multiple myeloma via the negative regulation of the Wnt/β-catenin/BCL-9 signaling pathway.
Oncology reports, 2015Co-Authors: Zesong Yang, Haiting Yuan, Qiong Liu, Jianbin ChenAbstract:The tumor suppressor protocadherin-10 (PCDH10) gene is important in cell proliferation, survival, apoptosis and migration. Inactivation of PCDH10 by promoter methylation is a frequent pathogenetic event in multiple myeloma (MM). The Wnt/β-catenin pathway is known to be involved in the cell growth of various types of cancer, including MM. However, the relationship between PCDH10 and Wnt signaling in MM remains unclear. In this study, we found that PCDH10 deficiency highly enhanced MM cell proliferation, Wnt signaling and the expression of BCL-9, an essential coactivator of Wnt transcriptional activity that is correlated with cell growth, survival and drug resistance. Restoration of PCDH10 suppressed nuclear localization of β-catenin, the activity of LEF/TCF, the expression of BCL-9 and AKT, whereas the expression of GSK3β was increased. The antagonistic effect of PCDH10 was associated with G1-phase blockage. Collectively, PCDH10 antagonized MM cell proliferation via the downregulation of Wnt/β-catenin/BCL-9 signaling, whereas PCDH10 repressed the expression of AKT to promote the expression of GSK3β and then to restrain the activation of β-catenin. Thus, the results offer a novel preclinical rationale in order to explore PCDH10 as an effective and selective therapeutic strategy to eradicate MM cells.
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Nuclear factor-κB is involved in the protocadherin-10-mediated pro-apoptotic effect in multiple myeloma.
Molecular medicine reports, 2014Co-Authors: Zesong Yang, Qiong Liu, Xi Peng, Jianbin ChenAbstract:The gene encoding protocadherin-10 (PCDH10), a member of the cadherin superfamily, has been recently identified as a tumor suppressor gene (TSG). PCDH10 plays important roles in the apoptosis of tumor cells in some cancer types. However, the exact role of PCDH10 in multiple myeloma (MM) is largely unknown. Increasing evidence has suggested that the activation of nuclear factor-κB (NF-κB) is crucial for apoptosis in myeloma cells. In this study, we investigated the pro-apoptotic effect of PCDH10 on myeloma cells and whether this effect may involve inhibition of the NF-κB pathway. We report here, for the first time to the best of our knowledge, that PCDH10 markedly induces apoptosis of myeloma cells, accompanied by an increase in activated caspase-3 and poly-ADP‑ribose polymerase (PARP) levels, and inhibited expression of anti‑apoptotic proteins. We also demonstrate that PCDH10 inhibits the activation of NF-κB, by inhibiting the expression of the inhibitor of nuclear factor-κB (IκB) kinase subunits (IKKs) and the phosphorylation of IκBα. Moreover, the constitutive NF-κB DNA-binding activity and the expression of the NF-κB‑regulated proteins cyclooxygenase-2 (COX-2), vascular endothelial growth factor (VEGF) and intercellular adhesion molecule 1 (ICAM-1) were inhibited by PCDH10 in MM cells. These results suggest that PCDH10 induces myeloma cell apoptosis, probably by inhibiting the NF-κB pathway.
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Protocadherin-10 is involved in angiogenesis and methylation correlated with multiple myeloma.
International journal of molecular medicine, 2012Co-Authors: Zesong Yang, Qiong Liu, Jun-jun Song, Jianbin ChenAbstract:Protocadherin-10 (PCDH10) which is located at 4q28.3, is a member of the cadherin superfamily of cell adhesion molecules. PCDH10 is broadly expressed in normal adult, but nearly undetectable in multiple myeloma (MM) tissues and cell lines. Its promoter methylation was detected in virtually all the silenced or downregulated cell lines. The silencing of PCDH10 could be reversed by pharmacological demethylation, indicating a methylation-mediated mechanism. In the current study, we investigated 44 patients (23 females, 21 males), 77.27% (34/44) of whom presented high methylation of PCDH10. We found no associations between promoter hypermethylation and gender or age at the time of initial diagnosis. We also examined the role of PCDH10 as a mediator of MM cell proliferation, cell cycle progression, and its involvement in angiogenesis. Our results demonstrate that the PCDH10 gene is a target for epigenetic silencing in MM and provide a link between the dysregulation of angiogenesis and DNA methylation.
Zesong Yang - One of the best experts on this subject based on the ideXlab platform.
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PCDH10 inhibits cell proliferation of multiple myeloma via the negative regulation of the wnt β catenin bcl 9 signaling pathway
Oncology Reports, 2015Co-Authors: Zesong Yang, Haiting Yuan, Qiong Liu, Jianbin ChenAbstract:The tumor suppressor protocadherin-10 (PCDH10) gene is important in cell proliferation, survival, apoptosis and migration. Inactivation of PCDH10 by promoter methylation is a frequent pathogenetic event in multiple myeloma (MM). The Wnt/β-catenin pathway is known to be involved in the cell growth of various types of cancer, including MM. However, the relationship between PCDH10 and Wnt signaling in MM remains unclear. In this study, we found that PCDH10 deficiency highly enhanced MM cell proliferation, Wnt signaling and the expression of BCL-9, an essential coactivator of Wnt transcriptional activity that is correlated with cell growth, survival and drug resistance. Restoration of PCDH10 suppressed nuclear localization of β-catenin, the activity of LEF/TCF, the expression of BCL-9 and AKT, whereas the expression of GSK3β was increased. The antagonistic effect of PCDH10 was associated with G1-phase blockage. Collectively, PCDH10 antagonized MM cell proliferation via the downregulation of Wnt/β-catenin/BCL-9 signaling, whereas PCDH10 repressed the expression of AKT to promote the expression of GSK3β and then to restrain the activation of β-catenin. Thus, the results offer a novel preclinical rationale in order to explore PCDH10 as an effective and selective therapeutic strategy to eradicate MM cells.
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PCDH10 inhibits cell proliferation of multiple myeloma via the negative regulation of the Wnt/β-catenin/BCL-9 signaling pathway.
Oncology reports, 2015Co-Authors: Zesong Yang, Haiting Yuan, Qiong Liu, Jianbin ChenAbstract:The tumor suppressor protocadherin-10 (PCDH10) gene is important in cell proliferation, survival, apoptosis and migration. Inactivation of PCDH10 by promoter methylation is a frequent pathogenetic event in multiple myeloma (MM). The Wnt/β-catenin pathway is known to be involved in the cell growth of various types of cancer, including MM. However, the relationship between PCDH10 and Wnt signaling in MM remains unclear. In this study, we found that PCDH10 deficiency highly enhanced MM cell proliferation, Wnt signaling and the expression of BCL-9, an essential coactivator of Wnt transcriptional activity that is correlated with cell growth, survival and drug resistance. Restoration of PCDH10 suppressed nuclear localization of β-catenin, the activity of LEF/TCF, the expression of BCL-9 and AKT, whereas the expression of GSK3β was increased. The antagonistic effect of PCDH10 was associated with G1-phase blockage. Collectively, PCDH10 antagonized MM cell proliferation via the downregulation of Wnt/β-catenin/BCL-9 signaling, whereas PCDH10 repressed the expression of AKT to promote the expression of GSK3β and then to restrain the activation of β-catenin. Thus, the results offer a novel preclinical rationale in order to explore PCDH10 as an effective and selective therapeutic strategy to eradicate MM cells.
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Nuclear factor-κB is involved in the protocadherin-10-mediated pro-apoptotic effect in multiple myeloma.
Molecular medicine reports, 2014Co-Authors: Zesong Yang, Qiong Liu, Xi Peng, Jianbin ChenAbstract:The gene encoding protocadherin-10 (PCDH10), a member of the cadherin superfamily, has been recently identified as a tumor suppressor gene (TSG). PCDH10 plays important roles in the apoptosis of tumor cells in some cancer types. However, the exact role of PCDH10 in multiple myeloma (MM) is largely unknown. Increasing evidence has suggested that the activation of nuclear factor-κB (NF-κB) is crucial for apoptosis in myeloma cells. In this study, we investigated the pro-apoptotic effect of PCDH10 on myeloma cells and whether this effect may involve inhibition of the NF-κB pathway. We report here, for the first time to the best of our knowledge, that PCDH10 markedly induces apoptosis of myeloma cells, accompanied by an increase in activated caspase-3 and poly-ADP‑ribose polymerase (PARP) levels, and inhibited expression of anti‑apoptotic proteins. We also demonstrate that PCDH10 inhibits the activation of NF-κB, by inhibiting the expression of the inhibitor of nuclear factor-κB (IκB) kinase subunits (IKKs) and the phosphorylation of IκBα. Moreover, the constitutive NF-κB DNA-binding activity and the expression of the NF-κB‑regulated proteins cyclooxygenase-2 (COX-2), vascular endothelial growth factor (VEGF) and intercellular adhesion molecule 1 (ICAM-1) were inhibited by PCDH10 in MM cells. These results suggest that PCDH10 induces myeloma cell apoptosis, probably by inhibiting the NF-κB pathway.
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Protocadherin-10 is involved in angiogenesis and methylation correlated with multiple myeloma.
International journal of molecular medicine, 2012Co-Authors: Zesong Yang, Qiong Liu, Jun-jun Song, Jianbin ChenAbstract:Protocadherin-10 (PCDH10) which is located at 4q28.3, is a member of the cadherin superfamily of cell adhesion molecules. PCDH10 is broadly expressed in normal adult, but nearly undetectable in multiple myeloma (MM) tissues and cell lines. Its promoter methylation was detected in virtually all the silenced or downregulated cell lines. The silencing of PCDH10 could be reversed by pharmacological demethylation, indicating a methylation-mediated mechanism. In the current study, we investigated 44 patients (23 females, 21 males), 77.27% (34/44) of whom presented high methylation of PCDH10. We found no associations between promoter hypermethylation and gender or age at the time of initial diagnosis. We also examined the role of PCDH10 as a mediator of MM cell proliferation, cell cycle progression, and its involvement in angiogenesis. Our results demonstrate that the PCDH10 gene is a target for epigenetic silencing in MM and provide a link between the dysregulation of angiogenesis and DNA methylation.
Jianming Ying - One of the best experts on this subject based on the ideXlab platform.
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Clinical significance of PCDH10 promoter methylation in diffuse large B-cell lymphoma.
BMC cancer, 2017Co-Authors: Wenting Huang, Xuemin Xue, Ling Shan, Tian Qiu, Lei Guo, Jianming YingAbstract:PCDH10, one of the non-clustered protocadherins, is identified as a tumor suppressor gene in many tumors. Recently, promoter methylation of PCDH10 was found in diffuse large B-cell lymphoma (DLBCL) but not in normal lymph nodes, suggesting that its epigenetic aberrance is essential to the lymphomagenesis. However, there are few studies on the clinicopathological relevance and prognostic significance of PCDH10 methylation status in DLBCL. One hundred-seven cases of DLBCL between Jan 2009 and Jul 2010 were selected to extract genomic DNA and perform bisulfite modification. Their methylation status of PCDH10 promoter were accessed by methylation-specific PCR (MSP) with methylated and unmethylated primers. Analysis of overall survival and clinicopathological correlation were conducted. PCDH10 hypermethylation were found in 54.2% (58/107) of DLBCL cases, but only 12.5% (1/8) in reactive lymph node/follicular hyperplasia. In RCHOP-treated cohort, promoter methylation of PCDH10 is an independent prognostic indicator of worse overall survival (p = 0.017; HR 4.045; 95%CI 1.287–12.711) and worse progress-free survival (p = 0.014; HR 2.977; 95%CI 1.245–7.119). Whereas, PCDH10 hypermethylation wasn’t correlated with MYC translocation and cell of origin classification using Hans model. PCDH10 methylation status could serve as a valuable biomarker for risk classification, and a potential therapeutic target for demethylating drugs in DLBCL in the future.
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Methylation of protocadherin 10, a novel tumor suppressor, is associated with poor prognosis in patients with gastric cancer.
Gastroenterology, 2008Co-Authors: Yuen Yee Cheng, Qian Tao, Kin-fai Cheung, Cleo N.y. Lam, Hua Geng, Linwei Tian, Ying P. Wong, Joanna Tong, Jianming YingAbstract:Background & Aims By using methylation-sensitive representational difference analysis, we identified protocadherin 10 (PCDH10) , a gene that encodes a protocadherin and is silenced in a tumor-specific manner. We analyzed its epigenetic inactivation, biological effects, and prognostic significance in gastric cancer. Methods Methylation status was evaluated by combined bisulfite restriction analysis and bisulfite sequencing. The effects of PCDH10 re-expression were determined in growth, apoptosis, proliferation, and invasion assays. PCDH10 target genes were identified by complementary DNA microarray analysis. Results PCDH10 was silenced or down-regulated in 94% (16 of 17) of gastric cancer cell lines; expression levels were restored by exposure to demethylating agents. Re-expression of PCDH10 in MKN45 gastric cancer cells reduced colony formation in vitro and tumor growth in mice; it also inhibited cell proliferation ( P P P Fas, Caspase 8, Jun , and CDKN1A ; the antiproliferation gene FGFR ; and the anti-invasion gene HTATIP2 . PCDH10 methylation was detected in 82% (85 of 104) of gastric tumors compared with 37% (38 of 104) of paired nontumor tissues ( P PCDH10 methylation was higher in precancerous lesions (27 of 45; 60%) than in chronic gastritis samples (11 of 59; 19%) ( P PCDH10 methylation in adjacent nontumor areas had a significant decrease in overall survival. Kaplan–Meier survival curves showed that PCDH10 methylation was associated significantly with shortened survival in stage I–III gastric cancer patients. Conclusions PCDH10 is a gastric tumor suppressor; its methylation at early stages of gastric carcinogenesis is an independent prognostic factor.
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Frequent epigenetic silencing of protocadherin 10 by methylation in multiple haematologic malignancies
British journal of haematology, 2007Co-Authors: Jianming Ying, Zifen Gao, Gopesh Srivastava, Paul G. Murray, Hwee Koon Goh, Chai Yen Lim, Yajun Wang, Teresa Marafioti, David Y. MasonAbstract:Epigenetic silencing of tumour suppressor genes (TSG) inactivates TSG functions. Previously, we identified PCDH10 as a methylated TSG in carcinomas. Here, we detected its frequent silencing and methylation in lymphoma cell lines including 100% Burkitt, 100% diffuse large B cell, 86% Hodgkin, 100% nasal natural killer/T-cell lymphoma and 1/3 of leukaemia cell lines, and in primary tumours but not in normal peripheral blood mononuclear cells or lymph nodes. PCDH10 silencing could be reversed by demethylation with 5-aza-2'-deoxycytidine. Methylation was further detected in 14% of Hodgkin lymphoma sera. Thus, PCDH10 methylation is frequently involved in lymphomagenesis and could serve as a tumour-specific biomarker.
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functional epigenetics identifies a protocadherin PCDH10 as a candidate tumor suppressor for nasopharyngeal esophageal and multiple other carcinomas with frequent methylation
Oncogene, 2006Co-Authors: Jianming Ying, Qian Tao, Gopesh Srivastava, Paul G. Murray, T J Seng, Cordelia Langford, Sai Wah Tsao, Thomas C Putti, Anthony T C ChanAbstract:Protocadherins constitute the largest subgroup in the cadherin superfamily of cell adhesion molecules. Their major functions are poorly understood, although some are implicated in nervous system development. As tumor-specific promoter methylation is a marker for tumor suppressor genes (TSG), we searched for epigenetically inactivated TSGs using methylation-subtraction combined with pharmacologic demethylation, and identified the PCDH10 CpG island as a methylated sequence in nasopharyngeal carcinoma (NPC). PCDH10 is broadly expressed in all normal adult and fetal tissues including the epithelia, though at different levels. It resides at 4q28.3--a region with hemizygous deletion detected by array-CGH in NPC cell lines; however, PCDH10 itself is not located within the deletion. In contrast, its transcriptional silencing and promoter methylation were frequently detected in multiple carcinoma cell lines in a biallelic way, including 12/12 nasopharyngeal, 13/16 esophageal, 3/4 breast, 5/5 colorectal, 3/4 cervical, 2/5 lung and 2/8 hepatocellular carcinoma cell lines, but not in any immortalized normal epithelial cell line. Aberrant methylation was further frequently detected in multiple primary carcinomas (82% in NPC, 42-51% for other carcinomas), but not normal tissues. The transcriptional silencing of PCDH10 could be reversed by pharmacologic demethylation with 5-aza-2'-deoxycytidine or genetic demethylation with double knockout of DNMT1 and DNMT3B, indicating a direct epigenetic mechanism. Ectopic expression of PCDH10 strongly suppressed tumor cell growth, migration, invasion and colony formation. Although the epigenetic and genetic disruptions of several classical cadherins as TSGs have been well documented in tumors, this is the first report that a widely expressed protocadherin can also function as a TSG that is frequently inactivated epigenetically in multiple carcinomas.
Qiong Liu - One of the best experts on this subject based on the ideXlab platform.
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PCDH10 inhibits cell proliferation of multiple myeloma via the negative regulation of the wnt β catenin bcl 9 signaling pathway
Oncology Reports, 2015Co-Authors: Zesong Yang, Haiting Yuan, Qiong Liu, Jianbin ChenAbstract:The tumor suppressor protocadherin-10 (PCDH10) gene is important in cell proliferation, survival, apoptosis and migration. Inactivation of PCDH10 by promoter methylation is a frequent pathogenetic event in multiple myeloma (MM). The Wnt/β-catenin pathway is known to be involved in the cell growth of various types of cancer, including MM. However, the relationship between PCDH10 and Wnt signaling in MM remains unclear. In this study, we found that PCDH10 deficiency highly enhanced MM cell proliferation, Wnt signaling and the expression of BCL-9, an essential coactivator of Wnt transcriptional activity that is correlated with cell growth, survival and drug resistance. Restoration of PCDH10 suppressed nuclear localization of β-catenin, the activity of LEF/TCF, the expression of BCL-9 and AKT, whereas the expression of GSK3β was increased. The antagonistic effect of PCDH10 was associated with G1-phase blockage. Collectively, PCDH10 antagonized MM cell proliferation via the downregulation of Wnt/β-catenin/BCL-9 signaling, whereas PCDH10 repressed the expression of AKT to promote the expression of GSK3β and then to restrain the activation of β-catenin. Thus, the results offer a novel preclinical rationale in order to explore PCDH10 as an effective and selective therapeutic strategy to eradicate MM cells.
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PCDH10 inhibits cell proliferation of multiple myeloma via the negative regulation of the Wnt/β-catenin/BCL-9 signaling pathway.
Oncology reports, 2015Co-Authors: Zesong Yang, Haiting Yuan, Qiong Liu, Jianbin ChenAbstract:The tumor suppressor protocadherin-10 (PCDH10) gene is important in cell proliferation, survival, apoptosis and migration. Inactivation of PCDH10 by promoter methylation is a frequent pathogenetic event in multiple myeloma (MM). The Wnt/β-catenin pathway is known to be involved in the cell growth of various types of cancer, including MM. However, the relationship between PCDH10 and Wnt signaling in MM remains unclear. In this study, we found that PCDH10 deficiency highly enhanced MM cell proliferation, Wnt signaling and the expression of BCL-9, an essential coactivator of Wnt transcriptional activity that is correlated with cell growth, survival and drug resistance. Restoration of PCDH10 suppressed nuclear localization of β-catenin, the activity of LEF/TCF, the expression of BCL-9 and AKT, whereas the expression of GSK3β was increased. The antagonistic effect of PCDH10 was associated with G1-phase blockage. Collectively, PCDH10 antagonized MM cell proliferation via the downregulation of Wnt/β-catenin/BCL-9 signaling, whereas PCDH10 repressed the expression of AKT to promote the expression of GSK3β and then to restrain the activation of β-catenin. Thus, the results offer a novel preclinical rationale in order to explore PCDH10 as an effective and selective therapeutic strategy to eradicate MM cells.
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Nuclear factor-κB is involved in the protocadherin-10-mediated pro-apoptotic effect in multiple myeloma.
Molecular medicine reports, 2014Co-Authors: Zesong Yang, Qiong Liu, Xi Peng, Jianbin ChenAbstract:The gene encoding protocadherin-10 (PCDH10), a member of the cadherin superfamily, has been recently identified as a tumor suppressor gene (TSG). PCDH10 plays important roles in the apoptosis of tumor cells in some cancer types. However, the exact role of PCDH10 in multiple myeloma (MM) is largely unknown. Increasing evidence has suggested that the activation of nuclear factor-κB (NF-κB) is crucial for apoptosis in myeloma cells. In this study, we investigated the pro-apoptotic effect of PCDH10 on myeloma cells and whether this effect may involve inhibition of the NF-κB pathway. We report here, for the first time to the best of our knowledge, that PCDH10 markedly induces apoptosis of myeloma cells, accompanied by an increase in activated caspase-3 and poly-ADP‑ribose polymerase (PARP) levels, and inhibited expression of anti‑apoptotic proteins. We also demonstrate that PCDH10 inhibits the activation of NF-κB, by inhibiting the expression of the inhibitor of nuclear factor-κB (IκB) kinase subunits (IKKs) and the phosphorylation of IκBα. Moreover, the constitutive NF-κB DNA-binding activity and the expression of the NF-κB‑regulated proteins cyclooxygenase-2 (COX-2), vascular endothelial growth factor (VEGF) and intercellular adhesion molecule 1 (ICAM-1) were inhibited by PCDH10 in MM cells. These results suggest that PCDH10 induces myeloma cell apoptosis, probably by inhibiting the NF-κB pathway.
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Protocadherin-10 is involved in angiogenesis and methylation correlated with multiple myeloma.
International journal of molecular medicine, 2012Co-Authors: Zesong Yang, Qiong Liu, Jun-jun Song, Jianbin ChenAbstract:Protocadherin-10 (PCDH10) which is located at 4q28.3, is a member of the cadherin superfamily of cell adhesion molecules. PCDH10 is broadly expressed in normal adult, but nearly undetectable in multiple myeloma (MM) tissues and cell lines. Its promoter methylation was detected in virtually all the silenced or downregulated cell lines. The silencing of PCDH10 could be reversed by pharmacological demethylation, indicating a methylation-mediated mechanism. In the current study, we investigated 44 patients (23 females, 21 males), 77.27% (34/44) of whom presented high methylation of PCDH10. We found no associations between promoter hypermethylation and gender or age at the time of initial diagnosis. We also examined the role of PCDH10 as a mediator of MM cell proliferation, cell cycle progression, and its involvement in angiogenesis. Our results demonstrate that the PCDH10 gene is a target for epigenetic silencing in MM and provide a link between the dysregulation of angiogenesis and DNA methylation.
Guosheng Ren - One of the best experts on this subject based on the ideXlab platform.
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Protocadherin 10 is frequently downregulated by promoter methylation and functions as a tumor suppressor gene in non-small cell lung cancer
Cancer biomarkers : section A of Disease markers, 2013Co-Authors: Xiaokui Tang, Xuedong Yin, Tingxiu Xiang, Li Chen, Guosheng RenAbstract:Abstract Purpose: Protocadherin 10 (PCDH10), a homophilic cell adhesion member of the protocadherin family, plays important roles in calcium-dependent cell-cell adhesion and signal transduction. PCDH10 expression is downregulated in a number of different malignances, predominantly through promoter methylation-driven silencing. This study was designed to investigate PCDH10 expression and promoter methylation status in non-small cell lung cancer (NSCLC), and biological effects of PCDH10 in lung cancer cells.Methods: The mRNA levels and promoter methylation status of PCDH10 were examined by RT-PCR and methylation-specific PCR (MSP) in lung cancer cell lines as well as primary lung tissue samples, and the clinical correlation of PCDH10 promoter methylation in NSCLC was further analyzed. The effects of PCDH10 re-expression in lung cancer cell lines was determined by cell proliferation, colony formation, and wound healing assays. Results: PCDH10 expression was downregulated or silenced in 4/8 lung cancer cell lines but could be restored by treatment with 5-aza-2'-deoxycytidine and trichostatin A. PCDH10 was also downregulated in NSCLC tissues compared to their corresponding adjacent tissues. Promoter methylation of PCDH10 was observed in 50% (20/40) of the NSCLC tissues but not in tumor-adjacent or normal tissues, and PCDH10 promoter methylation was statistically related to smoking. Ectopic expression of PCDH10 in silenced cells can reduce lung cancer cell proliferation and migration. Conclusion: PCDH10 is frequently downregulated by promoter methylation and may serve as a tumor suppressor gene (TSG) in NSCLC.
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Silencing of PCDH10 in hepatocellular carcinoma via de novo DNA methylation independent of HBV infection or HBX expression
Clinical and experimental medicine, 2012Co-Authors: Song Fang, Shifeng Huang, Ju Cao, Yang-an Wen, Liping Zhang, Guosheng RenAbstract:PCDH10 is a key tumor suppressive gene for nasopharyngeal, esophageal, and other carcinomas with frequent methylation. In this study, we investigated the potential epigenetic modification of the PCDH10 gene by hepatitis B virus × protein (HBx), a pivotal factor in the progression of HBV replication and potential carcinogenesis. PCDH10 expression was found to be down-regulated in 9/13 (69.2 %) of hepatocellular carcinoma (HCC) cell lines. Decreased PCDH10 expression was correlated with the methylation status of the PCDH10 promoter. Treatment with the DNA methyltransferase inhibitor 5-aza-2′-deoxycytidine (Aza) was sufficient to restore PCDH10 mRNA expression by suppressing PCDH10 promoter methylation in HepG2 cells. Treatment with Trichostatin A alone had no significant effect on PCDH10 expression but enhanced the effect of Aza. PCDH10 methylation was further detected in 76 % (38 of 50) of HCC tissues compared with 40 % (20 of 50) of paired adjacent tissues, with no methylation detected in normal human liver tissues. There were significant correlations between methylation status of PCDH10 and tumor size, serum AFP levels, metastasis or TNM staging (P < 0.05). Moreover, PCDH10 promoter methylation status was not associated with HBV infection in our panel of 50 primary HCC tumors, and transfection with HBX could not alter the status of PCDH10 promoter methylation. Collectively, these observations suggested that the expression of PCDH10 was silenced in HCC via de novo DNA methylation independent of HBV infection or HBX expression, and PCDH10 might form a potentially useful therapeutic target for HCC.