浙医Nature子刊 新肿瘤抑制基因

　　

生物通报道，浙江大学医学院附属邵逸夫医院生物医学研究中心，浙江省生物疗法重点实验室，中国南方国家重点肿瘤实验室，香港中文大学癌症研究所，李嘉诚健康科学研究中心的研究人员找到一个新的肿瘤抑制子，文章Phospholipase C delta 1 is a novel 3p22.3 tumor suppressor involved in cytoskeleton organization, with its epigenetic silencing correlated with high-stage gastric cancer在Nature子刊《Oncogene》在线版上发表。

 

文章通讯作者是来自浙江大学医学院的何超教授，目前任浙江大学医学院附属邵逸夫医院党委书记，肛肠外科主任医生，主要进行肿瘤的生物学治疗，大肠癌微转移，大肠肿瘤起源和转移的机制等研究。

何超等人发现，肿瘤抑制子基因座3p22上的PLCD1编码一种介导调节能量代谢信号，钙平衡和钙离子胞内移动信号的酶。通过鉴定发现PLCD1在胃癌发生机制中处于下游调节基因的地位，并通过表观遗传学模式来调节信号。

 

在正常的组织细胞中，PLCD1普遍表达，然而，在胃癌细胞中，其表达量显著下降，或是PLCD1被沉默（有84%被沉默，16/19），该基因的沉默与其富含CpG的单拷贝非甲基化的基因座的甲基化状态有关。

 

随后，研究人员在临床中发现，有62%（61/98）的胃癌患者原发性肿瘤细胞中CpG区域甲基化。这表明，PLCD1的甲基化是肿瘤生长期的一个表征。PLCD1失活会导致癌症的发生。深入的研究证实，PLCD1是一个具有功能性的胃癌肿瘤抑制子。

（生物通 小茜）

 

生物通推荐原文检索：Phospholipase C delta 1 is a novel 3p22.3 tumor suppressor involved in cytoskeleton organization, with its epigenetic silencing correlated with high-stage gastric cancer

 

X -T Hu1, F -B Zhang1, Y -C Fan2, X -S Shu2, A H Y Wong2, W Zhou3, Q -L Shi1, H -M Tang1, L Fu4, X -Y Guan4, S Y Rha5, Q Tao2 and C He1,3

 

1Biomedical Research Center, Sir Run Run Shaw Hospital, Zhejiang University and Key Laboratory of Biotherapy of Zhejiang Province, Hangzhou, China

2Cancer Epigenetics Laboratory, State Key Laboratory in Oncology in South China, Department of Clinical Oncology, Sir YK Pao Center for Cancer, Hong Kong Cancer Institute and Li Ka Shing Institute of Health Sciences, Chinese University of Hong Kong, Hong Kong

3Department of Colorectal Surgery, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, China

4Department of Clinical Oncology, University of Hong Kong, Hong Kong

5Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea

 

【Abstract】

Located at the important tumor suppressor locus, 3p22, PLCD1 encodes an enzyme that mediates regulatory signaling of energy metabolism, calcium homeostasis and intracellular movements. We identified PLCD1 as a downregulated gene in aerodigestive carcinomas through expression profiling and epigenetic characterization. We found that PLCD1 was expressed in all normal adult tissues but low or silenced in 84% (16/19) gastric cancer cell lines, well correlated with its CpG island (CGI) methylation status. Methylation was further detected in 62% (61/98) gastric primary tumors, but none of normal gastric mucosa tissues. PLCD1 methylation was significantly correlated with tumor high stage. Detailed methylation analysis of 37 CpG sites at the PLCD1 CGI by bisulfite genomic sequencing confirmed its methylation. PLCD1 silencing could be reversed by pharmacological demethylation with 5-aza-2'-deoxycytidine, indicating a direct epigenetic silencing. Ectopic expression of PLCD1 in silenced gastric tumor cells dramatically inhibited their clonogenicity and migration, possibly through downregulating MMP7 expression and hampering the reorganization of cytoskeleton through cofilin inactivation by phosphorylation. Thus, epigenetic inactivation of PLCD1 is common and tumor-specific in gastric cancer, and PLCD1 acts as a functional tumor suppressor involved in gastric carcinogenesis.

何超

肛肠外科主任医师，硕士生导师，党委书记。1982年毕业于原浙江医科大学。全国中西医结合协会肛肠分会副主委，浙江中西医结合协会副主委，浙江省医学会肛肠分会副主委，浙江省抗癌协会副主委。擅长大肠肛门良恶性肿瘤，炎症性疾病，先天性缺陷等诊治，熟悉肠镜下的微创手术，对复发性直肠癌和肛门疑难杂症有独到见解。 1982年毕业于原浙江医科。

 

研究方向 肿瘤的生物学治疗/大肠癌分子病理基础/大肠肿瘤的外科治疗  

 

现承担国家自然基金，省科技厅对外合作重点项目，省自然科学基金，省教委重大项目等多项课题，主要进行肿瘤的生物学治疗，大肠癌微转移，大肠肿瘤起源和转移的机制等研究，已发表SCI收录论文3篇，国家一级杂志5篇。现担任浙江大学医学院副院长，附属邵逸夫医院院长，全国中西医学会大肠肛门瘤分会副主任委员；浙江中西医学会副主任委员，肛肠外科分会主任委员；浙江省抗癌协会理事，大肠癌副主任委员。