CSIG promotes hepatocellular carcinoma proliferation by activating c-MYC expression.
CSIG promotes hepatocellular carcinoma proliferation by activating c-MYC expression.
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CSIG通过激活c-MYC表达促进肝细胞癌增殖
DOI：
10.18632/oncotarget.2900
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发表时间：
2015-03-10
期刊：
影响因子：
--
通讯作者：
Tong T
中科院分区：
文献类型：
--
作者：
Cheng Q;Yuan F;Lu F;Zhang B;Chen T;Chen X;Cheng Y;Li N;Ma L;Tong T
细胞衰老抑制基因（CSIG）蛋白显著延长了复制性衰老的进程，但其在肿瘤发生中的作用尚不清楚。为了揭示CSIG在HCC中的作用，我们测定了其在HCC组织及周围组织中的表达以及体外和体内对肿瘤细胞增殖的作用。CSIG蛋白在86.4%的人HCC癌组织中与匹配的周围组织相比过表达，且在HCC细胞中的表达高于未转化的肝细胞系L02。上调CSIG可显著增加SMMC7721和HepG2细胞的集落形成，沉默CSIG可诱导细胞周期阻滞和细胞凋亡。在小鼠异种移植瘤模型中证实了CSIG的致瘤能力。结果表明，CSIG能促进HepG2和SMMC7721细胞在体内的增殖。最后，CSIG蛋白直接与c-MYC蛋白相互作用，使c-MYC蛋白水平升高；随着CSIG的下调，c-MYC蛋白的泛素化和降解增加。CSIG在体内也能增加SMMC7721细胞中c-MYC蛋白的表达，并且注意到在大多数高CSIG的人癌组织中c-MYC蛋白水平也升高。
Cellular senescence-inhibited gene (CSIG) protein significantly prolongs the progression of replicative senescence, but its role in tumorigenesis is unclear. To reveal the role of CSIG in HCC, we determined its expression in HCC tissues and surrounding tissues and its functions in tumor cell proliferation in vitro and in vivo. CSIG protein was overexpressed in 86.4% of the human HCC cancerous tissues as compared with matched surrounding tissues, and its protein expression was greater in HCC cells than the non-transformed hepatic cell line L02. Furthermore, upregulation of CSIG significantly increased the colony formation of SMMC7721 and HepG2 cells, and silencing CSIG could induce cell cycle arrest and cell apoptosis. The tumorigenic ability of CSIG was confirmed in vivo in a mouse xenograft model. Our results showed that CSIG promoted the proliferation of HepG2 and SMMC7721 cells in vivo. Finally, CSIG protein directly interacted with c-MYC protein and increased c-MYC protein levels; the ubiquitination and degradation of c-MYC protein was increased with knockdown of CSIG. CSIG could also increase the expression of c-MYC protein in SMMC7721 cells in vivo, and it was noted that the level of c-MYC protein was also elevated in most human cancerous tissues with high level of CSIG.
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影响因子：
13.5
作者：
Cui, Chun-Ping;Zhang, Da-Jin;Wu, Chu-Tse
通讯作者：
Wu, Chu-Tse
影响因子：
2.8
作者：
Tsai, Wen-Chung;Chang, Hsiang-Ning;Pang, Jong-Hwei S.
通讯作者：
Pang, Jong-Hwei S.
影响因子：
8
作者：
Terradillos, O;Billet, O;Buendia, MA
通讯作者：
Buendia, MA
c-Myc 在人肝细胞癌中对 Glypican-3 的致癌激活
影响因子：
13.5
作者：
Li, Li;Jin, Ronghua;Chen, Dexi
通讯作者：
Chen, Dexi
影响因子：
4.7
作者：
Simile, MM;De Miglio, MR;Pascale, RM
通讯作者：
Pascale, RM