Elevated TRIM44 promotes intrahepatic cholangiocarcinoma progression by inducing cell EMT via MAPK signaling.
Elevated TRIM44 promotes intrahepatic cholangiocarcinoma progression by inducing cell EMT via MAPK signaling.
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TRIM44 升高通过 MAPK 信号传导诱导细胞 EMT，从而促进肝内胆管癌进展。
DOI：
10.1002/cam4.1313
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发表时间：
2018-03
期刊：
影响因子：
4
通讯作者：
Xu YP
中科院分区：
文献类型：
--
作者：
Peng R;Zhang PF;Zhang C;Huang XY;Ding YB;Deng B;Bai DS;Xu YP
肝内胆管细胞癌（ICC）的手术效果一直不理想，因为复发率高。本文研究了TRIM 44在人ICC中的表达及其作用。首先，通过Oncomine数据库分析TRIM 44在几种肿瘤中的表达，并检测其在ICC及相应癌旁组织中的mRNA和蛋白表达。其次，通过TRIM 44干扰和cDNA转染进一步研究TRIM 44在ICC细胞中的功能和作用机制。最后，通过Kaplan-Meier和考克斯回归评估TRIM 44的预后作用。我们发现，与相应的癌旁组织相比，TRIM 44在ICC组织中的表达上调，这与公共癌症数据库的结果一致。TRIM 44基因的敲除抑制了ICC细胞的侵袭和迁移，但增加了ICC细胞的凋亡。此外，高水平的TRIM 44显示诱导ICC细胞上皮向间充质转化（EMT）。在机制上，发现高水平的TRIM 44激活MAPK信号传导，并且MEK抑制剂AZD 6244逆转TRIM 44过表达赋予的细胞EMT和凋亡。TRIM 44表达与肿瘤大小（P = 0.035）、淋巴结转移（P = 0.008）和肿瘤分化程度（P = 0.036）呈正相关。重要的是，TRIM 44高组患者的总生存期较短，累积复发率高于TRIM 44低组患者。我们的研究结果表明，TRIM 44的升高通过诱导细胞EMT和凋亡抵抗促进ICC的发展，TRIM 44是一个有价值的预后生物标志物和有前途的治疗靶点ICC。
Surgical results for intrahepatic cholangiocarcinoma (ICC) remain unsatisfactory due to the high rate of recurrence. Here, we investigated that the expression and roles of tripartite motif‐containing protein 44 (TRIM44) in human ICCs. Firstly, TRIM44 expression was analyzed in several kinds of cancers by referring to public Oncomine database, and the expressions of TRIM44 mRNA and protein were tested in ICC and corresponding paratumorous tissues. Secondly, functions and mechanisms of TRIM44 in ICC cells were further evaluated by TRIM44 interference and cDNA transfection. Finally, the prognostic role of TRIM44 was assessed by Kaplan–Meier and Cox regression. We found that TRIM44 expression was upregulated in ICC tissues compared with corresponding paratumorous tissues, which were consistent with the results from the public cancer database. Knockdown of TRIM44 repressed the invasion and migration of ICC cells, while increased the ICC cell apoptosis. Additionally, high level of TRIM44 was shown to induce ICC cell epithelial to mesenchymal transition (EMT). Mechanistically, a high level of TRIM44 was found to activate MAPK signaling, and a MEK inhibitor, AZD6244, reversed cell EMT and apoptosis endowed by TRIM44 overexpression. Clinically, TRIM44 expression was positively associated with large tumor size (P = 0.035), lymphatic metastasis (P = 0.008) and poor tumor differentiation (P = 0.036). Importantly, patients in TRIM44high group had shorter overall survival and higher cumulative rate of recurrence than patients in TRIM44low group. Our results suggest elevated TRIM44 promotes ICC development by inducing cell EMT and apoptosis resistance, and TRIM44 is a valuable prognostic biomarker and promising therapeutic target of ICC.
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DOI：
10.1038/nri2413
发表时间：
2008-11
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
Ozato K;Shin DM;Chang TH;Morse HC 3rd
通讯作者：
Morse HC 3rd
影响因子：
3.4
作者：
Wang, Quan;Wen, Yu-Gang;Peng, Zhi-Hai
通讯作者：
Peng, Zhi-Hai
影响因子：
4.8
作者：
Deng, XM;Xiao, L;May, WS
通讯作者：
May, WS
DOI：
10.1016/j.bbrc.2009.04.010
发表时间：
2009-05-29
影响因子：
3.1
作者：
Urano, Tomohiko;Usui, Takahiko;Inoue, Satoshi
通讯作者：
Inoue, Satoshi
B-晶状体蛋白与 14-3-3 复合物诱导肝细胞癌上皮间质转化和索拉非尼耐药
影响因子：
13.5
作者：
Huang, Xiao-Yong;Ke, Ai-Wu;Zhou, Jian
通讯作者：
Zhou, Jian