Huo Qi, Ge Chao, Tian Hua, Sun Ji, Cui Meiling, Li Hong, Zhao Fangyu, Chen Taoyang, Xie Haiyang, Cui Ying, Yao Ming, Li Jinjun
State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Qi Dong Liver Cancer Institute, Qi Dong, China.
Cell Death Dis. 2017 May 4;8(5):e2766. doi: 10.1038/cddis.2017.165.
MDIG is known to be overexpressed in many types of human cancers and has demonstrated predictive power in the prognosis of cancer, although the functions and mechanisms of MDIG in liver cancer, especially in hepatocellular carcinoma (HCC), are still unknown. In this study, we report that MDIG and MYC were negatively regulated by IKZF1. MDIG overexpression substantially promoted HCC cell proliferation, cell migration and spreading, whereas knockdown of MDIG would reverse above-mentioned effect. MDIG effects on tumour cell growth were further demonstrated in a tumour xenograft model. Moreover, MDIG had effects on the level of p21(CIP1/WAF1) via H3K9me3 expression in HCC. MDIG was also found to be closely related to the sorafenib resistance of HCC cells in vitro. Clinically, we found that MDIG was frequently overexpressed in human HCCs (69.7%; n=155) and was significantly associated with histological grade and hepatitis B virus infection. Our findings indicate that MDIG plays an important role in HCC progression via MDIG/H3K9me3/p21(CIP1/WAF1) signalling and serves as a potential therapeutic target.
已知MDIG在多种人类癌症中过表达，并在癌症预后方面显示出预测能力，尽管MDIG在肝癌，尤其是肝细胞癌（HCC）中的功能和机制仍不清楚。在本研究中，我们报告MDIG和MYC受IKZF1负调控。MDIG过表达显著促进HCC细胞增殖、细胞迁移和扩散，而敲低MDIG可逆转上述效应。在肿瘤异种移植模型中进一步证实了MDIG对肿瘤细胞生长的影响。此外，MDIG通过HCC中H3K9me3表达影响p21（CIP1/WAF1）水平。还发现MDIG与体外HCC细胞对索拉非尼的耐药性密切相关。临床上，我们发现MDIG在人类HCC中经常过表达（69.7%；n = 155），并且与组织学分级和乙型肝炎病毒感染显著相关。我们的研究结果表明，MDIG通过MDIG/H3K9me3/p21（CIP1/WAF1）信号通路在HCC进展中起重要作用，并可作为潜在的治疗靶点。
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