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

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.