Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Warning: imagejpeg(C:\Inetpub\vhosts\kidney.de\httpdocs\phplern\28199980
.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Oncotarget
2017 ; 8
(9
): 15894-15911
Nephropedia Template TP
gab.com Text
Twit Text FOAVip
Twit Text #
English Wikipedia
PD-L1 up-regulation in melanoma increases disease aggressiveness and is mediated
through miR-17-5p
#MMPMID28199980
Audrito V
; Serra S
; Stingi A
; Orso F
; Gaudino F
; Bologna C
; Neri F
; Garaffo G
; Nassini R
; Baroni G
; Rulli E
; Massi D
; Oliviero S
; Piva R
; Taverna D
; Mandalà M
; Deaglio S
Oncotarget
2017[Feb]; 8
(9
): 15894-15911
PMID28199980
show ga
PD-L1 is expressed by a subset of patients with metastatic melanoma (MM) with an
unfavorable outcome. Its expression is increased in cells resistant to BRAF or
MEK inhibitors (BRAFi or MEKi). However, the function and regulation of
expression of PD-L1 remain incompletely understood.After generating BRAFi- and
MEKi-resistant cell lines, we observed marked up-regulation of PD-L1 expression.
These cells were characterized by a common gene expression profile with
up-regulation of genes involved in cell movement. Consistently, in vitro they
showed significantly increased invasive properties. This phenotype was controlled
in part by PD-L1, as determined after silencing the molecule. Up-regulation of
PD-L1 was due to post-transcriptional events controlled by miR-17-5p, which
showed an inverse correlation with PD-L1 mRNA. Direct binding between miR-17-5p
and the 3'-UTR of PD-L1 mRNA was demonstrated using luciferase reporter assays.In
a cohort of 80 BRAF-mutated MM patients treated with BRAFi or MEKi, constitutive
expression of PD-L1 in the absence of immune infiltrate, defined the patient
subset with the worst prognosis. Furthermore, PD-L1 expression increased in
tissue biopsies after the metastatic lesions became resistant to BRAFi or MEKi.
Lastly, plasmatic miR-17-5p levels were higher in patients with PD-L1+ than
PD-L1- lesions.In conclusion, our findings indicate that PD-L1 expression induces
a more aggressive behavior in melanoma cells. We also show that PD-L1
up-regulation in BRAFi or MEKi-resistant cells is partly due to
post-transcriptional mechanisms that involve miR-17-5p, suggesting that miR-17-5p
may be used as a marker of PD-L1 expression by metastatic lesions and ultimately
a predictor of responses to BRAFi or MEKi.
free
free
free
