Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0598934 (
tumor growth
)
58,965
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Although
MIR516A
has been reported to be downregulated and act as a tumor suppressor in multiple cancers, its expression and potential contribution to human bladder cancer (BC) remain unexplored. Unexpectedly, we showed here that
MIR516A
was markedly upregulated in human BC tissues and cell lines, while inhibition of
MIR516A
expression attenuated BC cell monolayer growth
in vitro
and xenograft
tumor growth
in vivo
, accompanied with increased expression of PHLPP2. Further studies showed that
MIR516A
was able to directly bind to the 3'-untranslated region of
PHLPP2
mRNA, which was essential for its attenuating PHLPP2 expression. The knockdown of
PHLPP2
expression in
MIR516A
-inhibited cells could reverse BC cell growth, suggesting that PHLPP2 is a
MIR516A
downstream mediator responsible for
MIR516A
oncogenic effect. PHLPP2 was able to mediate BECN1/Beclin1 stabilization indirectly, therefore promoting BECN1-dependent macroautophagy/autophagy, and inhibiting BC tumor cell growth. In addition, our results indicated that the increased autophagy by attenuating
MIR516A
resulted in a dramatic inhibition of xenograft tumor formation
in vivo
. Collectively, our results reveal that
MIR516A
has a novel oncogenic function in BC growth by directing binding to
PHLPP2
3'-UTR and inhibiting PHLPP2 expression, in turn at least partly promoting CUL4A-mediated BECN1 protein degradation, thereby attenuating autophagy and promoting BC growth, which is a distinct function of
MIR516A
identified in other cancers.
Abbreviation:
ATG3: autophagy related 3; ATG5: autophagy related 5; ATG7: autophagy related 7; ATG12: autophagy related 12; BAF: bafilomycin A
1
; BC: bladder cancer; CHX: cycloheximide; Co-IP: co-immunoprecipitation; CUL3: cullin 3; CUL4A: cullin 4A; CUL4B: cullin 4B; IF: immunofluorescence: IHC-p: immunohistochemistry-paraffin;
MIR516A
: microRNA 516a (microRNA 516a1 and microRNA 516a2); MS: mass spectrometry; PHLPP2:
PH domain and leucine rich repeat protein phosphatase
.
...
PMID:Oncogenic role of
MIR516A
in human bladder cancer was mediated by its attenuating PHLPP2 expression and BECN1-dependent autophagy. 3211 9
