Department of Infectious Disease, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
Department of Infectious Disease, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
Biochem Biophys Res Commun. 2019 Apr 16;511(4):889-895. doi: 10.1016/j.bbrc.2019.02.001. Epub 2019 Mar 5.
Tripartite motif-containing protein 7 (TRIM7), which is involved in the biosynthesis of glycogen, has been reported to drive lung tumorigenesis. In the present study, we aimed to examine the expression, roles and underlying molecular mechanisms of TRIM7 in hepatocellular carcinoma (HCC) development. Real-time PCR and immunohistochemical staining were performed to test the expression of TRIM7 in HCC tissues. Cell proliferation, cell cycle and tumorigenicity experiments were conducted to determine the function of TRIM7. The results showed that TRIM7 expression was elevated in human HCC tissues and that TRIM7 expression was significantly associated with tumor size, pTNM stage, serum α-fetoprotein (AFP) concentration, serum hepatitis B virus (HBV) DNA copy number and overall survival (OS) of HCC patients. TRIM7 knockdown inhibited the proliferation of HCC cells in vitro and in vivo. TRIM7 knockdown also induced a G1/S checkpoint in HCC cell lines. Additionally, TRIM7 knockdown led to decreased phosphorylated p38 (p-p38) and increased expression of p53 and p21. Ectopic expression of TRIM7 promoted HCC cell proliferation, cell cycle progression and p38 activation, but not in the presence of the p38 inhibitor SB203580. Moreover, TRIM7 overexpression enhanced the polyubiquitination and degradation of dual specificity phosphatase 6 (DUSP6). DUSP6 overexpression abolished the promotional effect of TRIM7 overexpression on HCC cell proliferation and the activation of p38. Furthermore, HBV X protein (HBx), a protein coded by HBV, was demonstrated to upregulate TRIM7 expression. Collectively, TRIM7 overexpression may contribute to the highly proliferative characteristics of HCC cells, and targeting TRIM7 might be a potential strategy for HCC treatment.
三结构域蛋白 7（TRIM7）参与糖原的生物合成，据报道可促进肺肿瘤发生。在本研究中，我们旨在研究 TRIM7 在肝细胞癌（HCC）发展中的表达、作用和潜在分子机制。通过实时 PCR 和免疫组织化学染色检测 HCC 组织中 TRIM7 的表达。进行细胞增殖、细胞周期和致瘤性实验以确定 TRIM7 的功能。结果显示，TRIM7 在人 HCC 组织中表达上调，并且 TRIM7 表达与肿瘤大小、pTNM 分期、血清 α-胎蛋白（AFP）浓度、血清乙型肝炎病毒（HBV）DNA 拷贝数和 HCC 患者的总生存（OS）显著相关。TRIM7 敲低抑制 HCC 细胞在体外和体内的增殖。TRIM7 敲低也诱导 HCC 细胞系中的 G1/S 检查点。此外，TRIM7 敲低导致磷酸化 p38（p-p38）减少和 p53 和 p21 的表达增加。TRIM7 的异位表达促进 HCC 细胞增殖、细胞周期进程和 p38 激活，但在 p38 抑制剂 SB203580 存在的情况下则不然。此外，TRIM7 过表达增强双特异性磷酸酶 6（DUSP6）的多泛素化和降解。DUSP6 过表达消除了 TRIM7 过表达对 HCC 细胞增殖和 p38 激活的促进作用。此外，乙型肝炎病毒 X 蛋白（HBx），一种由 HBV 编码的蛋白质，被证明可上调 TRIM7 的表达。总之，TRIM7 的过表达可能有助于 HCC 细胞的高增殖特征，靶向 TRIM7 可能是 HCC 治疗的一种潜在策略。
