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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 J+Biol+Chem
2016 ; 291
(40
): 21074-21084
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Suppression of MicroRNA-7 (miR-7) Biogenesis by Nuclear Factor 90-Nuclear Factor
45 Complex (NF90-NF45) Controls Cell Proliferation in Hepatocellular Carcinoma
#MMPMID27519414
Higuchi T
; Todaka H
; Sugiyama Y
; Ono M
; Tamaki N
; Hatano E
; Takezaki Y
; Hanazaki K
; Miwa T
; Lai S
; Morisawa K
; Tsuda M
; Taniguchi T
; Sakamoto S
J Biol Chem
2016[Sep]; 291
(40
): 21074-21084
PMID27519414
show ga
MicroRNA-7 (miR-7)has been characterized as an anti-oncogenic microRNA (miRNA) in
several cancers, including hepatocellular carcinoma (HCC). However, the mechanism
for the regulation of miR-7 production in tumors remains unclear. Here, we
identified nuclear factor 90 (NF90) and NF45 complex (NF90-NF45) as negative
regulators of miR-7 processing in HCC. Expression of NF90 and NF45 was
significantly elevated in primary HCC tissues compared with adjacent non-tumor
tissues. To examine which miRNAs are controlled by NF90-NF45, we performed an
miRNA microarray and quantitative RT-PCR analyses of HCC cell lines. Depletion of
NF90 resulted in elevated levels of mature miR-7, whereas the expression of
primary miR-7-1 (pri-miR-7-1) was decreased in cells following knockdown of NF90.
Conversely, the levels of mature miR-7 were reduced in cells overexpressing NF90
and NF45, although pri-miR-7-1 was accumulated in the same cells. Furthermore,
NF90-NF45 was found to bind pri-miR-7-1 in vitro These results suggest that
NF90-NF45 inhibits the pri-miR-7-1 processing step through the binding of
NF90-NF45 to pri-miR-7-1. We also found that levels of the EGF receptor, an
oncogenic factor that is a direct target of miR-7, and phosphorylation of AKT
were significantly decreased in HCC cell lines depleted of NF90 or NF45. Of note,
knockdown of NF90 or NF45 caused a reduction in the proliferation rate of HCC
cells. Taken together, NF90-NF45 stimulates an elevation of EGF receptor levels
via the suppression of miR-7 biogenesis, resulting in the promotion of cell
proliferation in HCC.