TP73-AS1 is induced by YY1 during TMZ treatment and highly expressed in the aging brain.

Aging
Gal MazorBarak Rotblat

Abstract

Aging is a factor associated with poor prognosis in glioblastoma (GBM). It is therefore important to understand the molecular features of aging contributing to GBM morbidity. TP73-AS1 is a long noncoding RNA (lncRNA) over expressed in GBM tumors shown to promote resistance to the chemotherapeutic temozolomide (TMZ), and tumor aggressiveness. How the expression of TP73-AS1 is regulated is not known, nor is it known if its expression is associated with aging. By analyzing transcriptional data obtained from natural and pathological aging brain, we found that the expression of TP73-AS1 is high in pathological and naturally aging brains. YY1 physically associates with the promoter of TP73-AS1 and we found that along with TP73-AS1, YY1 is induced by TMZ. We found that the TP73-AS1 promoter is activated by TMZ, and by YY1 over expression. Using CRISPRi to deplete YY1, we found that YY1 promotes up regulation of TP73-AS1 and the activation of its promoter during TMZ treatment. In addition, we identified two putative YY1 binding sites within the TP73-AS1 promoter, and used mutagenesis to find that they are essential for TMZ mediated promoter activation. Together, our data positions YY1 as an important TP73-AS1 regulator, demonstrating t...Continue Reading

References

Dec 1, 1993·Molecular and Cellular Biology·K J RiggsK Calame
Jun 5, 2002·Genome Research·W James KentDavid Haussler
Jul 9, 2004·Drug Metabolism Reviews·Vasilis VasiliouTia Estey
Aug 6, 2004·Proceedings of the National Academy of Sciences of the United States of America·Eva GrönroosJohan Ericsson
Mar 11, 2005·The New England Journal of Medicine·Roger StuppUNKNOWN National Cancer Institute of Canada Clinical Trials Group
Mar 11, 2005·The New England Journal of Medicine·Monika E HegiRoger Stupp
Jun 4, 2005·Nucleic Acids Research·Shannan J Ho SuiWyeth W Wasserman
Jun 20, 2007·Nucleic Acids Research·Shannan J Ho SuiWyeth W Wasserman
Sep 23, 2008·Genes & Development·Richard TomasiniTak W Mak
Oct 4, 2008·Proceedings of the National Academy of Sciences of the United States of America·Nicole C BerchtoldCarl W Cotman
Dec 14, 2011·Proceedings of the National Academy of Sciences of the United States of America·Massimiliano AgostiniGerry Melino
Sep 8, 2012·Nature·UNKNOWN ENCODE Project Consortium
Sep 8, 2012·Genome Research·Stephen G LandtMichael Snyder
Sep 14, 2012·G3 : Genes - Genomes - Genetics·Andrew T KwonWyeth W Wasserman
Sep 19, 2012·Genes & Development·Alessandro RufiniTak Wah Mak
Feb 19, 2013·Molecular Neurodegeneration·Badri VardarajanDavid Westaway
Apr 25, 2013·Nature Reviews. Cancer·João Pedro de Magalhães
Jul 3, 2013·Nature Cell Biology·Wenjing DuXiaolu Yang
Nov 5, 2013·Oncogene·I AmelioG Melino
Nov 6, 2013·Proceedings of the National Academy of Sciences of the United States of America·Maria Victoria Niklison-ChirouGerry Melino
Dec 3, 2014·Biochimica Et Biophysica Acta·Gabriel LeprivierPoul H Sorensen
Dec 24, 2014·Proceedings of the National Academy of Sciences of the United States of America·Ivano AmelioGerry Melino
Jan 3, 2015·Aging·Massimiliano AgostiniAlessandro Rufini
Jul 23, 2015·The Journal of Biological Chemistry·Gary Z Wang, Stephen P Goff
Oct 21, 2015·Biopreservation and Biobanking·Latarsha J CarithersUNKNOWN GTEx Consortium
May 27, 2016·Journal of Experimental & Clinical Cancer Research : CR·Samantha KaufholdBenjamin Bonavida
Aug 6, 2016·Neuroscience Letters·Erik LadomerskyDerek A Wainwright
Dec 30, 2016·Nature Reviews. Clinical Oncology·Guido ReifenbergerMichael Weller
Aug 18, 2017·Cell Death Discovery·Debra ToiberBarak Rotblat
Nov 11, 2017·Nucleic Acids Research·Carrie A DavisJ Michael Cherry
May 31, 2018·Proceedings of the National Academy of Sciences of the United States of America·Alberto MariniGerry Melino
Aug 5, 2018·Nature Communications·Zhongde YeJörg J Goronzy
Aug 9, 2018·Structure·Ivano Amelio, Gerry Melino
May 11, 2016·Genes & Diseases·Sang Y Lee
Dec 12, 2018·Aging·Piervito LoprioreIvano Amelio

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