microRNA-34a inhibits epithelial mesenchymal transition in human
cholangiocarcinoma by targeting Smad4 through transforming growth
factor-beta/Smad pathway
#MMPMID26077733
Qiao P
; Li G
; Bi W
; Yang L
; Yao L
; Wu D
BMC Cancer
2015[Jun]; 15
(?): 469
PMID26077733
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BACKGROUND: Extrahepatic Cholangiocarcinoma (EHCC) is one of the uncommon
malignancies in the digestive system which is characterized by a poor prognosis.
Aberrations of miRNAs have been shown involved in the progression of this
disease. In this study, we evaluated the expression and effects of miR-34a on
EHCC. METHODS: miR-34a expression levels were detected in EHCC tissues, adjacent
non-tumor tissues, normal bile duct (NBD) specimens of patients and
cholangiocarcinoma (CC) cell lines by quantitative real-time polymerase chain
reaction (qRT-PCR). Relationships between miR-34a with clinical characteristics
of EHCC patients were further analyzed. Computational search, functional
luciferase assay and western blot were further used to demonstrate the downstream
target of miR-34a in CC cells. Immunohistochemistry was carried on to identify
the downstream target gene of miR-34a in EHCC patients. Cell morphology, invasion
and migration assays were further applied to confirm the anti-carcinogenic
effects of miR-34a through the downstream target. RESULTS: miR-34a expression was
significantly decreased in human EHCC tissues and CC cell lines when compared
with the adjacent non-tumor tissues and normal bile duct tissues. miR-34a was
found correlated with the migration and invasion in EHCC patients. Smad4 was
over-expressed in most of the EHCC patients and was further demonstrated as one
of the downstream targets of miR-34a, which was involved in the progression of
EHCC. Moreover, activation of miR-34a suppressed invasion and migration through
TGF-beta/Smad4 signaling pathway by epithelial-mesenchymal transition (EMT) in
vitro. CONCLUSIONS: Taken together, our results suggest that miR-34a inhibits
invasion and migration by targeting Smad4 to suppress EMT through TGF- beta/Smad
signaling pathway in human EHCC.
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