PSMG3‐AS1 enhances glioma resistance to temozolomide via stabilizing c‐Myc in the nucleus. Issue 5 (5th April 2022)

• Record Type: Journal Article
• Authors: Zhou, Li; Huang, Xuming; Zhang, Yu; Wang, Jihui; Li, Haiyan; Huang, Haiwei
• Is Part Of: Brain and behavior. Volume 12:Issue 5(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-04-05
• Subjects: chemotherapy resistance -- c‐Myc -- long non‐coding RNA (LncRNA) -- PSMG3‐AS1 -- temozolomide; Neurology -- Periodicals; Neurosciences -- Periodicals; Psychology -- Periodicals; Psychiatry -- Periodicals; 616.8005
• DOI: 10.1002/brb3.2531
• Languages: English
• ISSNs: 2162-3279

Abstract

Abstract: Glioblastoma (GBM) is the main form of primary brain malignancies with a dismal prognosis partly due to its invasive growth and rapid relapse. GBM frequently developed resistance to current standard‐of‐care therapeutic modalities, including surgery, radiation and chemotherapy, of which temozolomide (TMZ) is the most widely used first‐line anti‐GBM drug. Despite the intense efforts of the past decades, the underlying mechanisms of GBM resistance to TMZ remain largely unclear. Here we show that the long noncoding RNA (lncRNA) PSMG3‐AS1 is significantly upregulated in GBM and its expression correlates with the grade of glioma, with the highest level observed in GBM (Grade IV glioma). We also demonstrated that PSMG3‐AS1 mediates the resistance of GBM to TMZ, as knockdown of PSMG3‐AS1 remarkably increased the sensitivity whereas overexpression of PSMG3‐AS1 in sensitive GBM cell line induced a resistance phenotype to TMZ. Mechanistically, PSMG3‐AS1 directly binds to c‐Myc and thus stabilizes c‐Myc in the nucleus to promote the survival of GBM cells under treatment of TMZ. Our data demonstrated an unreported role of PSMG3‐AS1 in TMZ resistance and provide a potential novel target to tackle TMZ resistance in GBM. Abstract : The mechanisms unraveled in this study might provide novel targets to overcome resistance to TMZ and bring benefits to GBM patients. The identification of PSMG3‐AS1 would also be beneficial to the pathological determination of resistance of GBM to TMZ in clinic