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CUL4A facilitates hepatocarcinogenesis by promoting cell cycle progression and
epithelial-mesenchymal transition
#MMPMID26593394
Pan Y
; Wang B
; Yang X
; Bai F
; Xu Q
; Li X
; Gao L
; Ma C
; Liang X
Sci Rep
2015[Nov]; 5
(?): 17006
PMID26593394
show ga
CUL4A, a member of the CULLIN family, functions as a scaffold protein for an E3
ubiquitin ligase. It was reported that the CUL4A gene showed amplification in
some human primary hepatocellular carcinomas (HCC). However, the exact role of
CUL4A in HCC remains unknown. Here, we aimed to investigate the expression and
function of CUL4A in HCC development. Through immunohistochemistry study, we
showed increased CUL4A expression in HCC tissues. Statistical analysis disclosed
an inverse correlation between CUL4A expression and tumor differentiation grade,
and patient survival, but a positive correlation with hepatocyte proliferation as
well as lymphatic and venous invasion. CUL4A expression in HCC tissues was
associated with HBeAg status in patients and upregulated by HBV in HCC cell
lines. Further functional assay showed that CUL4A overexpression significantly
promoted growth of H22 tumor homografts in BALB/c mice. Consistently, CUL4A
knockdown inhibited the proliferation of established HCC cells, accompanied by
S-phase reduction and Cyclin A and Cyclin B1 repression. Furthermore, CUL4A siRNA
ameliorated the motility of HCC cell lines with altered expression of
epithelial-mesenchymal transition (EMT)-associated molecules. Taken together, our
findings indicate that CUL4A plays a pivotal role in HCC progression and may
serve as a potential marker for clinical diagnosis and target for therapy.
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