Oncostatin-M differentially regulates mesenchymal and proneural signature genes in gliomas via STAT3 signaling

Neoplasia : an International Journal for Oncology Research
Kumar NateshPadma Shastry

Abstract

Glioblastoma (GBM), the most malignant of the brain tumors is classified on the basis of molecular signature genes using TCGA data into four subtypes- classical, mesenchymal, proneural and neural. The mesenchymal phenotype is associated with greater aggressiveness and low survival in contrast to GBMs enriched with proneural genes. The proinflammatory cytokines secreted in the microenvironment of gliomas play a key role in tumor progression. The study focused on the role of Oncostatin-M (OSM), an IL-6 family cytokine in inducing mesenchymal properties in GBM. Analysis of TCGA and REMBRANDT data revealed that expression of OSMR but not IL-6R or LIFR is upregulated in GBM and has negative correlation with survival. Amongst the GBM subtypes, OSMR level was in the order of mesenchymal > classical > neural > proneural. TCGA data and RT-PCR analysis in primary cultures of low and high grade gliomas showed a positive correlation between OSMR and mesenchymal signature genes-YKL40/CHI3L1, fibronectin and vimentin and a negative correlation with proneural signature genes-DLL3, Olig2 and BCAN. OSM enhanced transcript and protein level of fibronectin and YKL-40 and reduced the expression of Olig2 and DLL3 in GBM cells. OSM-regulated mesench...Continue Reading

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Citations

Apr 9, 2016·Molecular Therapy : the Journal of the American Society of Gene Therapy·Jian ZhengYunhui Liu
Sep 24, 2016·Molecular Neurobiology·Zangbéwendé Guy OuédraogoEmmanuel Chautard
Feb 27, 2018·The Journal of Clinical Investigation·Marni B SiegelCharles M Perou
Dec 7, 2018·Expert Opinion on Biological Therapy·Jan AdamowiczTomasz Drewa
Jan 30, 2019·Journal of Cellular Physiology·Qing GuoAn-Hua Wu
Jan 18, 2020·BioMed Research International·Qinglin LiuWandong Su
Nov 24, 2017·Journal of Neuro-oncology·Wen WangJizong Zhao
Nov 15, 2020·International Immunopharmacology·Ali MasjediFarhad Jadidi-Niaragh
Feb 3, 2021·Infection and Immunity·Katrina E TraberLee J Quinton

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Methods Mentioned

BETA
enzymatic dissociation
transfection
transfections
PCR
electrophoresis
zymography

Software Mentioned

REMBRANDT
Molecular BRAin Neoplasia DaTa ( REMBRANDT )
Agilent
Image J
Photoshop
Affymatrix

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