Tripartite motif 31 promoted hepatocellular carcinoma progression by inducing ubiquitination of TSC1-TSC2 complex
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- 英文论文题名：Tripartite motif 31 promoted hepatocellular carcinoma progression by inducing ubiquitination of TSC1-TSC2 complex
- 论文作者：Han Lihui ; Guo Pengbo ; Ma Xiaomin ; Li Tao ; Zhao Wei ; Qiu Yumin ; Ma Xiaoxiao ; Zhu Lihui ; Lin Yueke
- 英文论文作者：Han Lihui ; Guo Pengbo ; Ma Xiaomin ; Li Tao ; Zhao Wei ; Qiu Yumin ; Ma Xiaoxiao ; Zhu Lihui ; Lin Yueke ; Department of Immunology ; Shandong University School of Medicine
- 年：2016
- 作者机构：Department of Immunology,Shandong University School of Medicine;
- 英文论文关键词：Tripartite motif 31 ; TSC1-TSC2 complex ; ubiquitin degradation ; hepatocellular carcinoma
- 会议召开时间：2016-11-04
- 会议录名称：第十一届全国免疫学学术大会摘要汇编
- 英文会议录名称：Abstracts of 2016 CSI Congress on Immunology
- 语种：英文
- 分类号：R735.7
- 学会代码：IGMD
- 会议名称：第十一届全国免疫学学术大会
- 会议地点：中国安徽合肥
- 主办单位：中国免疫学会
- 学会名称：中国免疫学会
- 页数：2
- 文件大小：1333k
- 原文格式：D
- 会议级别：全国
摘要
Objective: Tripartite motif(TRIM) 31 is a member of the tripartite motif-containing protein family, which is involved in a broad range of biological and pathological processes. However,the role of TRIM31 in hepatocellular carcinoma(HCC) progression remains to be clarified. We aim to define the role of TRIM31 in the progression of HCC and its involved molecular mechanism.Methods: Liver cancer tissues and paired non-cancerous liver tissues from HCC patients were collected to detect the expression of TRIM31 by western blot and immunohistochemistry(IHC). HCC cells were transfected with TRIM31 plasmid or small interference RNA for the gain and loss of function assay of the effect of TRIM31 on HCC cells. Western blot and immunoprecipitation assay were used for detection of the signaling pathway and molecular target of TRIM31 inHCC progression. Results: Our data showed that expression of TRIM31 was significantly upregulated in HCC tissues and its overexpression was significantly correlated with advanced disease status. Both gain and loss of function assay verified that TRIM31 promoted the malignant behaviors of HCC cells through over-activation of mTORC1-HIF-1α pathway. Further analyses demonstrated that TRIM31 directly bound to the tuberous sclerosis complex(TSC) 1 and TSC2 complex, promoted the E3 ligase mediated K48-linked ubiquitination and degradation of this complex. Exogenous overexpression of TSC1 and TSC2 efficiently rescued TRIM31-induced malignant behaviors of HCC cells, thus verified that TRIM31 exerted its tumor-promoter effect by inhibiting TSC1 and TSC2 complex. Conclusion: Our study revealed a novel molecular mechanism of HCC progression and indicated a novel therapeutic strategy against HCC by targeting TRIM31.
Objective: Tripartite motif(TRIM) 31 is a member of the tripartite motif-containing protein family, which is involved in a broad range of biological and pathological processes. However,the role of TRIM31 in hepatocellular carcinoma(HCC) progression remains to be clarified. We aim to define the role of TRIM31 in the progression of HCC and its involved molecular mechanism.Methods: Liver cancer tissues and paired non-cancerous liver tissues from HCC patients were collected to detect the expression of TRIM31 by western blot and immunohistochemistry(IHC). HCC cells were transfected with TRIM31 plasmid or small interference RNA for the gain and loss of function assay of the effect of TRIM31 on HCC cells. Western blot and immunoprecipitation assay were used for detection of the signaling pathway and molecular target of TRIM31 inHCC progression. Results: Our data showed that expression of TRIM31 was significantly upregulated in HCC tissues and its overexpression was significantly correlated with advanced disease status. Both gain and loss of function assay verified that TRIM31 promoted the malignant behaviors of HCC cells through over-activation of mTORC1-HIF-1α pathway. Further analyses demonstrated that TRIM31 directly bound to the tuberous sclerosis complex(TSC) 1 and TSC2 complex, promoted the E3 ligase mediated K48-linked ubiquitination and degradation of this complex. Exogenous overexpression of TSC1 and TSC2 efficiently rescued TRIM31-induced malignant behaviors of HCC cells, thus verified that TRIM31 exerted its tumor-promoter effect by inhibiting TSC1 and TSC2 complex. Conclusion: Our study revealed a novel molecular mechanism of HCC progression and indicated a novel therapeutic strategy against HCC by targeting TRIM31.
Objective: Tripartite motif(TRIM) 31 is a member of the tripartite motif-containing protein family, which is involved in a broad range of biological and pathological processes. However,the role of TRIM31 in hepatocellular carcinoma(HCC) progression remains to be clarified. We aim to define the role of TRIM31 in the progression of HCC and its involved molecular mechanism.Methods: Liver cancer tissues and paired non-cancerous liver tissues from HCC patients were collected to detect the expression of TRIM31 by western blot and immunohistochemistry(IHC). HCC cells were transfected with TRIM31 plasmid or small interference RNA for the gain and loss of function assay of the effect of TRIM31 on HCC cells. Western blot and immunoprecipitation assay were used for detection of the signaling pathway and molecular target of TRIM31 inHCC progression. Results: Our data showed that expression of TRIM31 was significantly upregulated in HCC tissues and its overexpression was significantly correlated with advanced disease status. Both gain and loss of function assay verified that TRIM31 promoted the malignant behaviors of HCC cells through over-activation of mTORC1-HIF-1α pathway. Further analyses demonstrated that TRIM31 directly bound to the tuberous sclerosis complex(TSC) 1 and TSC2 complex, promoted the E3 ligase mediated K48-linked ubiquitination and degradation of this complex. Exogenous overexpression of TSC1 and TSC2 efficiently rescued TRIM31-induced malignant behaviors of HCC cells, thus verified that TRIM31 exerted its tumor-promoter effect by inhibiting TSC1 and TSC2 complex. Conclusion: Our study revealed a novel molecular mechanism of HCC progression and indicated a novel therapeutic strategy against HCC by targeting TRIM31.
引文