Enhanced MAPK signaling drives ETS1-mediated induction of miR-29b leading to downregulation of TET1 and changes in epigenetic modifications in a subset of lung SCC.

Oncogene
M A TaylorC M Chresta

Abstract

Non-small-cell lung cancer is the leading cause of cancer death worldwide and is comprised of several histological subtypes, the two most common being adenocarcinoma (AC) and squamous cell carcinoma (SCC). Targeted therapies have successfully improved response rates in patients with AC tumors. However, the majority of SCC tumors lack specific targetable mutations, making development of new treatment paradigms for this disease challenging. In the present study, we used iterative non-negative matrix factorization, an unbiased clustering method, on mRNA expression data from the cancer genome atlas (TCGA) and a panel of 24 SCC cell lines to classify three disease segments within SCC. Analysis of gene set enrichment and drug sensitivity identified an immune-evasion subtype that showed increased sensitivity to nuclear factor-κB and mitogen-activated protein kinase (MAPK) inhibition, a replication-stress associated subtype that showed increased sensitivity to ataxia telangiectasia inhibition, and a neuroendocrine-associated subtype that showed increased sensitivity to phosphoinositide 3-kinase and fibroblast growth factor receptor inhibition. Additionally, each of these subtypes exhibited a unique microRNA expression profile. Focusing...Continue Reading

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Citations

Jul 15, 2016·Chinese Medical Journal·Yi-Ping TianMao-De Lai
Nov 2, 2017·Oncotarget·Shilpa Thakur, Charles Brenner
Jan 24, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Vaishali Bhardwaj, Abul Kalam Azad Mandal
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Feb 28, 2021·Chromosome Research : an International Journal on the Molecular, Supramolecular and Evolutionary Aspects of Chromosome Biology·Mohit JainShambhudeo D Kharde
Aug 28, 2021·International Journal of Molecular Sciences·Lukas GeislerChristoph Roderburg

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Datasets Mentioned

BETA
GDC0941

Methods Mentioned

BETA
transfection
RNA-seq
PCR

Software Mentioned

R
ACTViewer
GSEA
R package gplots
NMF
Omics Explorer
Omics Explorer ( Qlucore
Graph Pad Prism
Ingenuity Pathway Analysis software
AgiMicroRna

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