The Oncogenic Role of Tribbles 1 in Hepatocellular Carcinoma Is Mediated by a Feedback Loop Involving microRNA-23a and p53.

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