The Oncogenic Role of Tribbles 1 in Hepatocellular Carcinoma Is Mediated by a Feedback Loop Involving microRNA-23a and p53.
The Oncogenic Role of Tribbles 1 in Hepatocellular Carcinoma Is Mediated by a Feedback Loop Involving microRNA-23a and p53.
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Tribbles 1 在肝细胞癌中的致癌作用是由涉及 microRNA-23a 和 p53 的反馈环介导的
DOI：
10.3389/fphys.2017.00789
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发表时间：
2017
影响因子：
4
通讯作者：
Wang J
中科院分区：
文献类型：
--
作者：
Ye Y;Wang G;Wang G;Zhuang J;He S;Song Y;Ni J;Xia W;Wang J
肝细胞癌（Hepatocellular carcinoma，HCC）是一种常见的恶性肿瘤，复发转移率高，预后差。在这里，我们研究了假激酶Tribbles 1（TRIB 1），一种与几种恶性肿瘤相关的支架蛋白，在HCC中的参与，并研究了潜在的机制。TRIB 1在HCC组织和细胞系中上调，与低水平的p53相关。TRIB 1功能获得和丧失实验表明，TRIB 1促进HCC细胞活力伴随着p53的下调，并诱导HCC细胞迁移、侵袭和上皮-间质转化。TRIB 1被鉴定为microRNA-23 a（miR-23 a）的靶点，并且miR-23 a过表达在HCC细胞中下调TRIB 1并上调p53。TRIB 1的异位表达以p53依赖的方式上调β-catenin及其效应子c-myc和MMP-7。TRIB 1沉默通过涉及p53和β-连环蛋白信号转导的调节的机制抑制肿瘤生长并促进体内细胞凋亡。目前的研究结果表明，TRIB 1通过一个反馈回路促进HCC肿瘤发生和侵袭，该反馈回路涉及miR-23 a对其表达的调节，可能下调p53，并表明β-catenin信号通路的参与。这些发现提示了HCC治疗的潜在靶点，因此值得进一步研究。
Hepatocellular carcinoma (HCC) is a common malignancy associated with a high risk of recurrence and metastasis and a poor prognosis. Here, we examined the involvement of the pseudokinase Tribbles 1 (TRIB1), a scaffold protein associated with several malignancies, in HCC and investigated the underlying mechanisms. TRIB1 was upregulated in HCC tissues and cell lines in correlation with low levels of p53. TRIB1 gain and loss of function experiments indicated that TRIB1 promoted HCC cell viability concomitant with the downregulation of p53, and induced HCC cell migration, invasion, and epithelial-mesenchymal transition. TRIB1 was identified as a target of microRNA-23a (miR-23a), and miR-23a overexpression downregulated TRIB1 and upregulated p53 in HCC cells. Ectopic expression of TRIB1 upregulated β-catenin and its effectors c-myc and MMP-7 in a p53-dependent manner. TRIB1 silencing inhibited tumor growth and promoted apoptosis in vivo via a mechanism that would involve the modulation of p53 and β-catenin signaling. The present results indicate that TRIB1 promotes HCC tumorigenesis and invasiveness via a feedback loop that involves the modulation of its expression by miR-23a with the likely downregulation of p53, and suggest the involvement of the β-catenin signaling pathway. These findings suggest potential targets for the treatment of HCC and therefore merit further investigation.
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影响因子：
37.3
作者：
Chen L;Li M;Li Q;Wang CJ;Xie SQ
通讯作者：
Xie SQ
影响因子：
37.3
作者：
Chhabra R;Dubey R;Saini N
通讯作者：
Saini N
DOI：
10.1016/j.bpg.2014.08.007
发表时间：
2014-10-01
影响因子：
3.2
作者：
Bosetti, Cristina;Turati, Federica;La Vecchia, Carlo
通讯作者：
La Vecchia, Carlo
DOI：
10.1016/j.clinre.2013.12.002
发表时间：
2014-06-01
影响因子：
2.7
作者：
Bao, Lidao;Zhao, Jianfen;Ren, Xianhua
通讯作者：
Ren, Xianhua
影响因子：
64.5
作者：
Kruse JP;Gu W
通讯作者：
Gu W