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Overexpression of SLC34A2 is an independent prognostic indicator in bladder
cancer and its depletion suppresses tumor growth via decreasing c-Myc expression
and transcriptional activity
#MMPMID28151475
Ye W
; Chen C
; Gao Y
; Zheng ZS
; Xu Y
; Yun M
; Weng HW
; Xie D
; Ye S
; Zhang JX
Cell Death Dis
2017[Feb]; 8
(2
): e2581
PMID28151475
show ga
Solute carrier family 34 member 2 (SLC34A2), a pH-sensitive sodium-dependent
phosphate transporter, is associated with several human cancers. In this study,
we investigate the clinical significance of SLC34A2 and its function in human
bladder cancer (BC). The expression dynamics of SLC34A2 were examined in two
independent cohorts of BC samples by quantitative PCR, western blotting and
immunohistochemical staining. In the training cohort (156 cases), we applied the
X-tile program software to assess the optimal cutoff points for biomarkers in
order to accurately classify patients according to clinical outcome. In the
validation cohort (130 cases), the cutoff score derived from X-title analysis was
investigated to determine the association of SLC34A2 expression with survival
outcome. A series of in vitro and in vivo assays were then performed to elucidate
the function of SLC34A2 in BC and its underlying mechanisms. Results showed that
SLC34A2 was significantly upregulated in BC cell lines and clinical samples. In
both two cohorts of BC samples, high expression of SLC34A2 was associated with
large tumor size, advanced T status and poor patients' survival. The depletion of
SLC34A2 in BC suppressed cellular viability, colony formation and
anchorage-independent growth in vitro, and inhibited xenograft tumor growth in
vivo, whereas overexpression of SLC34A2 had the converse effect. Simultaneously,
downregulation of SLC34A2 decreased the transcriptional activity and protein
expression level of c-Myc in BC cells, whereas restoration of c-Myc expression
could compromise the anti-proliferation effect of SLC34A2 depletion. Furthermore,
miR-214 was proved as a negative regulator of SLC34A2. Our present study
illustrated that SLC34A2 has an important role in promoting proliferation and
tumorigenicity of BC, and may represent a novel therapeutic target for this
disease.
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