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2017 ; 9
(5
): 2457-2465
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MicroRNA-199a-3p inhibits tumorigenesis of hepatocellular carcinoma cells by
targeting ZHX1/PUMA signal
#MMPMID28559996
Guan J
; Liu Z
; Xiao M
; Hao F
; Wang C
; Chen Y
; Lu Y
; Liang J
Am J Transl Res
2017[]; 9
(5
): 2457-2465
PMID28559996
show ga
BACKGROUND AND OBJECTIVE: MicroRNAs play an important role in cell proliferation,
apoptosis, differentiation, and invasion by regulating the expression of various
genes. For example, the downregulation of microRNA-199a-3p (miR-199a-3p) that is
noted in numerous human malignancies, including hepatocellular carcinoma (HCC),
results in a poor prognosis in patients with HCC. This finding suggests that
miR-199a-3p overexpression in HCC could provide a new treatment approach. We
explored this possibility by examining the effects of miR-199a-3p on the growth
and apoptosis of HCC cells in vitro and vivo. METHODS: The miR-199a-3p signaling
pathway was examined using ZHX1 (zinc-fingers and homeoboxes-1) or PUMA (a p53
upregulated modulator of apoptosis) siRNA transfection to determine the effects
of miR-199a-3p on growth and apoptosis of HepG2 cells in vitro. A subcutaneously
implanted tumor model of HepG2 cells in nude mice was used to assess the effects
of miR-199a-3p on the signaling pathway and tumorigenesis development in vivo.
RESULTS: miR-199a-3p inhibited growth and induced apoptosis of HepG2 cells in
vitro. These effects were accompanied by upregulation of ZHX1 and PUMA. Targeting
ZHX1 inhibited upregulation of PUMA after miR-199a-3p transfection. In addition,
miR-199a-3p inhibited Bcl2 expression, but increased Bax and cleaved caspase-3
expression. Targeting PUMA or ZHX1 reversed the effect of miR-199a-3p, followed
by upregulation of Bcl2 and downregulation of Bax and cleaved caspase-3,
respectively. Furthermore, miR-199a-3p inhibited tumorigenesis of xenografts in
nude mice. CONCLUSIONS: miRNA-199a-3p could effectively prevent primary tumor
formation. The ability of this therapy to decrease tumorigenesis may be related
toZHX1-dependent PUMA signals.