Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=27821157
&cmd=llinks): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests
in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 215
Let-7 inhibits self-renewal of hepatocellular cancer stem-like cells through
regulating the epithelial-mesenchymal transition and the Wnt signaling pathway
#MMPMID27821157
Jin B
; Wang W
; Meng XX
; Du G
; Li J
; Zhang SZ
; Zhou BH
; Fu ZH
BMC Cancer
2016[Nov]; 16
(1
): 863
PMID27821157
show ga
BACKGROUND: Tumor suppressive let-7 miRNAs are universally down-regulated in
human hepatocellular carcinoma (HCC) versus normal tissues; however, the roles
and related molecular mechanisms of let-7 in HCC stem cells are poorly
understood. METHODS: We examined the inhibitory effect of let-7 miRNAs on the
proliferation of MHCC97-H and HCCLM3 hepatic cancer cells by using MTT
(3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, which was
further confirmed by apoptosis and cell cycle studies. The sphere-forming assay
was used to study the effects of let-7a on stem like cells. Through western blot,
immunofluorescence and the luciferase-reporter assay, we explored the activity of
epithelial-mesenchymal transition (EMT) signaling factors in HCC cells. qRT-PCR
was applied to detect miRNA expression levels in clinical tissues. RESULTS:
Let-7a effectively repressed cell proliferation and viability, and in stem-like
cells, also let-7a decreased the efficiency of sphere formation.in stem-like
cells. The suppression of EMT signaling factors in HCC cells contributed to
let-7's induced tumor viability repression and Wnt activation repression.
Besides, Wnt1 is critical and essential for let-7a functions, and the rescue with
recombinant Wnt1 agent abolished the suppressive roles of let-7a on
hepatospheres. In clinical HCC and normal tissues, let-7a expression was
inversely correlated with Wnt1 expression. CONCLUSIONS: Let-7 miRNAs, especially
let-7a, will be a promising therapeutic strategy in the treatment of HCC through
eliminating HCC stem cells, which could be achieved by their inhibitory effect on
the Wnt signaling pathway.
free
free
free
