is Induced by YY1 During TMZ Treatment and Highly Expressed in the Aging Brain

Overview

Journal Aging (Albany NY)

Specialty Geriatrics

Date 2021 Jun 11

PMID 34115613

Citations 2

Authors

Gal Mazor

Dmitri Smirnov

Hila Ben David

Ekaterina Khrameeva

Debra Toiber

Barak Rotblat

Affiliations

Soon will be listed here.

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. 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 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 is high in pathological and naturally aging brains. YY1 physically associates with the promoter of and we found that along with , is induced by TMZ. We found that the promoter is activated by TMZ, and by YY1 over expression. Using CRISPRi to deplete YY1, we found that YY1 promotes up regulation of and the activation of its promoter during TMZ treatment. In addition, we identified two putative YY1 binding sites within the promoter, and used mutagenesis to find that they are essential for TMZ mediated promoter activation. Together, our data positions YY1 as an important regulator, demonstrating that is expressed in the natural and pathological aging brain, including during neurodegeneration and cancer. Our findings advance our understanding of expression, bringing forth a new link between TMZ resistance and aging, both of which contribute to GBM morbidity.

Citing Articles

Inhibiting lncRNA NEAT1 Increases Glioblastoma Response to TMZ by Reducing Connexin 43 Expression.

Liang J, Xie J, He J, Li Y, Wei D, Zhou R Cancer Rep (Hoboken). 2024; 7(10):e70031.

PMID: 39453684 PMC: 11505515. DOI: 10.1002/cnr2.70031.

Crosstalk between YY1 and lncRNAs in cancer: A review.

Wang X, Li J, Cao Y Medicine (Baltimore). 2023; 101(49):e31990.

PMID: 36626426 PMC: 9750593. DOI: 10.1097/MD.0000000000031990.

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