MicroRNA-142-3p is involved in regulation of MGMT expression in glioblastoma cells

• Published in: Cancer management and research Vol. 10; pp. 775 - 785
• Main Authors: Lee, Yi-Yen, Yarmishyn, Aliaksandr A, Wang, Mong-Lien, Chen, Hsiao-Yun, Chiou, Shih-Hwa, Yang, Yi-Ping, Lin, Chun-Fu, Huang, Pin-I, Chen, Yi-Wei, Ma, Hsin-I, Chen, Ming-Teh
• Format: Journal Article
• Language: English
• Published: New Zealand Dove Medical Press Limited 01.01.2018; Taylor & Francis Ltd; Dove Medical Press
• Subjects: Angiogenesis; Biochemistry; Brain cancer; Brain research; Brain tumors; Cancer; Cancer therapies; Cancer treatment; carmustine (BCNU); Cell death; Chemotherapy; Cytotoxicity; Deoxyribonucleic acid; Diagnosis; DNA; DNA methylation; DNA repair; Dosage and administration; Drug therapy; Drugs; Enzymes; Gene expression; Genes; Genetic aspects; Glioblastoma (GBM); Glioblastomas; Gliomas; Guanine; Managers; Medical prognosis; Messenger RNA; MicroRNA; microRNA-142-3p (miR-142-3p); MicroRNAs; O6-methylguanine-DNA methyltransferase (MGMT); Original Research; Penicillin; Purines; RNA; Surgery; Systematic review; Target recognition; Temozolomide; temozolomide (TMZ); Transferases; Tumors; United States > US; carmustine; temozolomide; glioblastoma; miR-142-3p; O6-methylguanine-DNA methyltransferase
• ISSN: 1179-1322; 1179-1322
• DOI: 10.2147/CMAR.S157261

Glioblastoma multiforme (GBM) is the most malignant brain tumor, and there is no effective treatment strategy. Patients with GBM have a median overall survival of only 14.6 months. Current treatment consists of safe and maximal surgical excision, followed by concurrent chemoradiotherapy and maintenance chemotherapy. There are several obstacles that hinder the effectiveness of this aggressive treatment. Temozolomide (TMZ) is an oral alkylating drug that acts through alkylating the position of guanine in DNA that leads to cell death. However, the expression and enzymatic activity of the DNA repair protein MGMT limits the therapeutic benefit from treatment with TMZ. MGMT reduces the efficacy of alkylating drugs by removing the methyl or alkyl group from damaged -methylguanine. Expression levels of play an important role in the outcome of GBM patients. miRNAs are a group of small regulatory RNAs that control target gene expression by binding to mRNAs. miR-142-3p has been found to be an important factor in the development and maintenance of the oncogenic state. In this study, we sought to investigate whether miR-142-3p can regulate gene expression in GBM cells. Here, we show that miR-142-3p downregulates expression through binding to the 3'-UTR of mRNA, thus affecting protein translation. Responsiveness to TMZ was significantly enhanced after transfection with miR-142-3p. Overexpression of miR-142-3p also sensitized GBM cells to alkylating drugs. Above all, our findings demonstrate that miR-142-3p plays a critical role in regulating expression, has great potential for future clinical applications, and acts as a new diagnostic marker for this intractable disease.