Upregulated TRIM11 Exerts its Oncogenic Effects in Hepatocellular Carcinoma Through Inhibition of P53
Upregulated TRIM11 Exerts its Oncogenic Effects in Hepatocellular Carcinoma Through Inhibition of P53
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DOI：
10.1159/000484678
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发表时间：
2017-01-01
影响因子：
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通讯作者：
Wang, Xiongbiao
中科院分区：
文献类型：
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作者：
Liu, Jinjin;Rao, Jun;Wang, Xiongbiao
背景/目的：含有三重基序（TRIM）家族在肿瘤的发生和进展中发挥着至关重要的作用。然而，对于TRIM11在肝细胞癌（HCC）中的功能和机制知之甚少。方法：通过实时PCR、Western blot和免疫组织化学（IHC）染色检测TRIM11的表达水平。通过慢病毒感染产生TRIM11敲低细胞，并使用MTT、集落形成测定、迁移和侵袭测定等功能测定以及异种移植肿瘤模型来研究TRIM11在HCC中的作用。我们还确定了 TRIM11 对 p53 信号传导及其下游分子的影响。结果：我们发现HCC组织中TRIM11 mRNA和蛋白水平较正常组织显着升高；水平升高与患者生存率低相关。通过功能丧失和获得的研究，TRIM11 的敲低可抑制细胞增殖、迁移、体外侵袭和体内肿瘤生长。此外，TRIM11 负向调节 p53 表达。 p53 的敲除消除了 TRIM11 shRNA 在 HCC 细胞中的体外和体内生物学功能。结论：这些数据表明 TRIM11 通过在体外和体内下调 p53 在 HCC 中发挥致癌作用。我们的数据为 HCC 的发病机制提供了新的见解，并表明 TRIM11 可能作为 HCC 治疗的新治疗靶点。 (c) 2017 年作者由 S. Karger AG 出版，巴塞尔
Background/Aims: The tripartite motif containing (TRIM) family plays crucial roles in tumor development and progression. However, little is known about the function and mechanism of TRIM11 in hepatocellular carcinoma (HCC). Methods: The expression levels of TRIM11 were examined by real-time PCR, Western blot and Immunohistochemical (IHC) staining. TRIM11 knockdown cells were produced by lentivirus infection, and functional assays, such as MTT, colony formation assay, migration and invasion assays and a xenograft tumor model were used to investigate the role of TRIM11 in HCC. We also determined the effect of TRIM11 on p53 signaling and its downstream molecules. Results: We found that TRIM11 mRNA and protein levels were significantly increased in HCC tissues as compared with normal tissues; increased levels correlated with poor patient survival. By loss-and gain-of-function investigations, knockdown of TRIM11 suppressed cell proliferation, migration, invasion in vitro and tumor growth in vivo. Moreover, TRIM11 negatively regulated p53 expression. Knockdown of p53 abrogated the in vitro and in vivo biological functions of TRIM11 shRNA in HCC cells. Conclusions: These data show that TRIM11 exerts its oncogenic effect in HCC by downregulating p53 both in vitro and in vivo. Our data provide new insights into the pathogenesis of HCC and indicate that TRIM11 may serve as a new therapeutic target for HCC treatment. (c) 2017 The Author(s) Published by S. Karger AG, Basel