Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=24926545
&cmd=llinks): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests
in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 215
Frequent coamplification and cooperation between C-MYC and PVT1 oncogenes promote
malignant pleural mesothelioma
#MMPMID24926545
Riquelme E
; Suraokar MB
; Rodriguez J
; Mino B
; Lin HY
; Rice DC
; Tsao A
; Wistuba II
J Thorac Oncol
2014[Jul]; 9
(7
): 998-1007
PMID24926545
show ga
INTRODUCTION: Malignant pleural mesothelioma (MPM) is a deadly disease with poor
prognosis and few treatment options. We characterized and elucidated the roles of
C-MYC and PVT1 involved in the pathogenesis of MPM. METHODS: We used small
interfering RNA (siRNA)-mediated knockdown in MPM cell lines to determine the
effect of C-MYC and PVT1 abrogation on MPM cells undergoing apoptosis,
proliferation, and cisplatin sensitivity. We also characterized the expression of
microRNAs spanning the PVT1 region in MPM cell lines. Copy number analysis was
measured by quantitative polymerase chain reaction and fluorescence in situ
hybridization. RESULTS: Copy number analysis revealed copy number gains (CNGs) in
chromosomal region 8q24 in six of 12 MPM cell lines. MicroRNA analysis showed
high miR-1204 expression in MSTO-211H cell lines with four copies or more of
PVT1. Knockdown by siRNA showed increased PARP-C levels in MSTO-211H transfected
with siPVT1 but not in cells transfected with siC-MYC. C-MYC and PVT1 knockdown
reduced cell proliferation and increased sensitivity to cisplatin. Analysis of
the expression of apoptosis-related genes in the MSTO-211H cell line suggested
that C-MYC maintains a balance between proapoptotic and antiapoptotic gene
expression, whereas PVT1 and, to a lesser extent, miR-1204 up-regulate
proapoptotic genes and down-regulate antiapoptotic genes. Fluorescence in situ
hybridization analysis of MPM tumor specimens showed a high frequency of both
CNGs (11 of 75) and trisomy (three copies; 11 of 75) for the C-MYC locus.
CONCLUSION: Our results suggest that C-MYC and PVT1 CNG promotes a malignant
phenotype of MPM, with C-MYC CNG stimulating cell proliferation and PVT1 both
stimulating proliferation and inhibiting apoptosis.
free
free
free
