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2017 ; 8
(ä): 789
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The Oncogenic Role of Tribbles 1 in Hepatocellular Carcinoma Is Mediated by a
Feedback Loop Involving microRNA-23a and p53
#MMPMID29176948
Ye Y
; Wang G
; Wang G
; Zhuang J
; He S
; Song Y
; Ni J
; Xia W
; Wang J
Front Physiol
2017[]; 8
(ä): 789
PMID29176948
show ga
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 ?-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
?-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 ?-catenin signaling pathway. These findings suggest
potential targets for the treatment of HCC and therefore merit further
investigation.