Tripartite motif containing 62 is a novel prognostic marker and suppresses tumor metastasis via c-Jun/Slug signaling-mediated epithelial-mesenchymal transition in cervical cancer.
Tripartite motif containing 62 is a novel prognostic marker and suppresses tumor metastasis via c-Jun/Slug signaling-mediated epithelial-mesenchymal transition in cervical cancer.
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DOI：
10.1186/s13046-016-0445-5
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发表时间：
2016-10-28
期刊：
影响因子：
--
通讯作者：
Yao SZ
中科院分区：
文献类型：
--
作者：
Liu TY;Chen J;Shang CL;Shen HW;Huang JM;Liang YC;Wang W;Zhao YH;Liu D;Shu M;Guo LY;Hu Z;Yao SZ
TRIM62(包含62个三方基序)已被发现对几种癌症具有肿瘤抑制作用。然而，它在宫颈癌(CC)中的确切生物学作用和相关机制尚不清楚。采用实时定量聚合酶链式反应和免疫印迹方法检测TRIM62mRNA和蛋白在人CC细胞系和组织中的表达。采用免疫组织化学方法检测30例正常宫颈和189例宫颈鳞癌组织中TRIM62的表达。采用单因素和多因素COX回归分析及Kaplan-Meier生存分析，探讨TRIM62表达与CC患者预后的关系。通过体外和体内实验研究TRIM62对癌细胞生长和转移的影响。利用多途径报告基因阵列识别TRIM62可能操纵的信号转导途径。TRIM62在人CC细胞和组织中经常下调。癌组织中TRIM62的低表达与癌组织的侵袭性相关。此外，TRIM62也是CC患者术后总体和无病生存的独立不良预后因素。此外，在CC细胞中增强表达TRIM62可显著抑制其体外增殖、迁移和侵袭能力。此外，皮下移植瘤模型和小鼠移植瘤模型均显示TRIM62抑制了肿瘤的生长和转移。进一步的机制研究表明，TRIM62可能通过抑制c-jun/slug信号转导抑制上皮-间充质转化(EMT)。TRIM62对肿瘤细胞增殖的抑制作用可能是通过靶向c-jun来调节细胞周期相关蛋白Cyclin D1和P27。TRIM62是一种潜在的CC预后生物标志物，可通过抑制c-jun/slug信号转导途径抑制CC的转移。本文的在线版本(doi：10.1186/s13046-0160445-5)包含补充材料，授权用户可以使用。
TRIM62 (tripartite motif containing 62) has been found to act as a tumor suppressor of several cancers. However, its precise biological role and related mechanism remain unknown in cervical cancer (CC). Quantitative Real-time PCR and western blot were adopted to detect the mRNA and protein expression level of TRIM62 in both human CC cell lines and tissues. Immunohistochemistry was used to measure the TRIM62 expression in 30 normal cervical and 189 CC tissues. Univariate and multivariate Cox regression analyses and Kaplan–Meier survival analyses performed to investigate the association between TRIM62 expression and CC patients’ prognosis. The effect of TRIM62 on CC growth and metastasis was studied in vitro and in vivo. Multi-pathway reporter array were utilized to identify the potential signaling manipulated by TRIM62. TRIM62 was frequently down-regulated in both human CC cells and tissues. Low expression of TRIM62 in CC tissues was associated with aggressive clinicopathological features of CC patients. In addition, TRIM62 was also an independent poor prognostic factor for overall and disease-free survival of CC patients after surgery. Moreover, enforced expression of TRIM62 in CC cells significantly inhibited their abilities of proliferation, migration and invasion in vitro. Besides, subcutaneous xenograft tumor model and xenograft mouse metastatic model respectively displayed that TRIM62 impeded the growth and metastasis of CC in vivo. Furthermore, mechanism study exhibited that TRIM62 could suppress epithelial-mesenchymal transition (EMT) by inhibiting c-Jun/Slug signaling. The inhibitory role of TRIM62 in tumor proliferation might be through regulating cell cycle related proteins CyclinD1 and P27 by targeting c-Jun. TRIM62 is a potential prognostic biomarker in CC and suppresses metastasis of CC via inhibiting c-Jun/Slug signaling-mediated EMT. The online version of this article (doi:10.1186/s13046-016-0445-5) contains supplementary material, which is available to authorized users.
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