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2017 ; 36
(1
): 127
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Nucleolar and spindle associated protein 1 promotes the aggressiveness of
astrocytoma by activating the Hedgehog signaling pathway
#MMPMID28899410
Wu X
; Xu B
; Yang C
; Wang W
; Zhong D
; Zhao Z
; He L
; Hu Y
; Jiang L
; Li J
; Song L
; Zhang W
J Exp Clin Cancer Res
2017[Sep]; 36
(1
): 127
PMID28899410
show ga
BACKGROUND: The prognosis of human astrocytoma is poor, and the molecular
alterations underlying its pathogenesis still needed to be elucidated. Nucleolar
and spindle associated protein 1 (NUSAP1) was observed in several types of
cancers, but its role in astrocytoma remained unknown. METHODS: The expression of
NUSAP1 in astrocytoma cell lines and tissues were measured with western blotting
and Real-Time PCR. Two hundred and twenty-one astrocytoma tissue samples were
analyzed by immunochemistry to demonstrate the correlation between the NUSAP1
expression and clinicopathological characteristics. 3-(4,5-dimethylthiazol-2-yl)
2,5-diphenyltetrazolium bromide (MTT) assay, colony formation, transwell matrix
penetration assay, wound healing assay and anchorage-independent growth assay
were used to investigate the biological effect of NUSAP1 in astrocytoma. An
intracranial brain xenograft tumor model was used to confirm the oncogenic role
of NUSAP1 in human astrocytoma. Luciferase reporter assay was used to investigate
the effect of NUSAP1 on Hedgehog signaling pathway. RESULTS: NUSAP1 was markedly
overexpressed in astrocytoma cell lines and tissues compared with normal
astrocytes and brain tissues. NUSAP1 was found to be overexpressed in 152 of 221
(68.78%) astrocytoma tissues, and was significantly correlated to poor survival.
Further, ectopic expression or knockdown of NUSAP1 significantly promoted or
inhibited, respectively, the invasive ability of astrocytoma cells. Moreover,
intracranial xenografts of astrocytoma cells engineered to express NUSAP1 were
highly invasive compared with the parental cells. With regard to its molecular
mechanism, upregulation of NUSAP1 in astrocytoma cells promoted the nuclear
translocation of GLI family zinc finger 1 (GLI1) and upregulated the downstream
genes of the Hedgehog pathway. CONCLUSION: These findings indicate that NUSAP1
contributes to the progression of astrocytoma by enhancing tumor cell
invasiveness via activation of the Hedgehog signaling pathway, and that NUSAP1
might be a potential prognostic biomarker as well as a target in astrocytoma.