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2017 ; 17
(1
): 644
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Integrator complex subunit 6 (INTS6) inhibits hepatocellular carcinoma growth by
Wnt pathway and serve as a prognostic marker
#MMPMID28899352
Lui KY
; Zhao H
; Qiu C
; Li C
; Zhang Z
; Peng H
; Fu R
; Chen HA
; Lu MQ
BMC Cancer
2017[Sep]; 17
(1
): 644
PMID28899352
show ga
BACKGROUND: Integrator complex subunit 6 (INTS6) was found to play a tumour
suppressing role in certain types of solid tumours. In this study, we wanted to
determine the expression level of INTS6 in hepatocellular carcinoma (HCC) and
evaluate its clinical characteristics and mechanisms in HCC patients (Lui and Lu,
European Journal of Cancer, 51:S94, 2015). METHODS: First, we used a microarray
analysis to explore the mRNA expression levels in HCC and paired normal liver
tissues; second, we used qRT-PCR to measure the INTS6 mRNA levels in a cohort of
50 HCC tissues and adjacent normal liver tissues; third, we used Western blot
analyses to detect the INTS6 protein levels in 20 paired HCC and normal liver
tissues; fourth, we used immunohistochemistry to determine the INTS6 expression
levels in 70 archived paraffin-embedded HCC samples. Finally, we investigated the
suppressive function of INTS6 in the Wnt pathway. RESULTS: Herein, according to
the microarray data analysis, the expression levels of INTS6 were dramatically
down-regulated in HCC tissues vs. those in normal liver tissues (p<0.05). qRT-PCR
and Western blot analyses showed that the INTS6 mRNA and protein expression was
significantly down-regulated in tumour tissues compared to the adjacent normal
liver tissues (p<0.05). Immunohistochemical assays revealed that decreased INTS6
expression was present in 62.9% (44/70) of HCC patients. Correlation analyses
showed that INTS6 expression was significantly correlated with serum
alpha-fetoprotein levels (AFP, p =0.004), pathology grade (p =0.005), and tumour
recurrence (p =0.04). Kaplan-Meier analysis revealed that patients with low INTS6
expression levels had shorter overall and disease-free survival rates than
patients with high INTS6 expression levels (p =0.001 and p =0.001). Multivariate
regression analysis indicated that INTS6 was an independent predictor of overall
survival and disease-free survival rates. Mechanistically, INTS6 increased WIF-1
expression and then inhibited the Wnt/?-catenin signalling pathway. CONCLUSION:
The results of our study show that down-regulated INTS6 expression is associated
with a poorer prognosis in HCC patients. This newly identified INTS6/WIF-1 axis
indicates the molecular mechanism of HCC and may represent a therapeutic target
in HCC patients.
|Adaptor Proteins, Signal Transducing/*genetics
[MESH]