MicroRNA-142-3p is involved in regulation of MGMT expression in glioblastoma cells
Yi-Yen Lee,1,2,* Aliaksandr A Yarmishyn,3,4,* Mong-Lien Wang,3,4 Hsiao-Yun Chen,4,5 Shih-Hwa Chiou,3–5 Yi-Ping Yang,4,5 Chun-Fu Lin,1,2 Pin-I Huang,2,6 Yi-Wei Chen,2,6 Hsin-I Ma,7 Ming-Teh Chen1,2 1Department of Neurosurgery, Neurological Institute, Taipei Veterans General Hospital, 2Facul...
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| Format: | Article |
| Language: | English |
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Dove Medical Press
2018-04-01
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| Series: | Cancer Management and Research |
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| Online Access: | https://www.dovepress.com/microrna-142-3p-is-involved-in-regulation-of-mgmt-expression-in-gliobl-peer-reviewed-article-CMAR |
| _version_ | 1818683892308115456 |
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| author | Lee YY Yarmishyn AA Wang ML Chen HY Chiou S Yang YP Lin C Huang PI Chen YW Ma HI Chen M |
| author_facet | Lee YY Yarmishyn AA Wang ML Chen HY Chiou S Yang YP Lin C Huang PI Chen YW Ma HI Chen M |
| author_sort | Lee YY |
| collection | DOAJ |
| description | Yi-Yen Lee,1,2,* Aliaksandr A Yarmishyn,3,4,* Mong-Lien Wang,3,4 Hsiao-Yun Chen,4,5 Shih-Hwa Chiou,3–5 Yi-Ping Yang,4,5 Chun-Fu Lin,1,2 Pin-I Huang,2,6 Yi-Wei Chen,2,6 Hsin-I Ma,7 Ming-Teh Chen1,2 1Department of Neurosurgery, Neurological Institute, Taipei Veterans General Hospital, 2Faculty of Medicine, National Yang-Ming University, 3Institute of Pharmacology, National Yang-Ming University, 4Department of Medical Research, Taipei Veterans General Hospital, 5Institute of Clinical Medicine, National Yang Ming University, 6Cancer Center, Radiation Oncology Division, Taipei Veterans General Hospital, 7Department of Neurological Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan *These authors contributed equally to this work Background: 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 O6 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 O6-methylguanine. Expression levels of MGMT 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. Results: In this study, we sought to investigate whether miR-142-3p can regulate MGMT gene expression in GBM cells. Here, we show that miR-142-3p downregulates MGMT expression through binding to the 3′-UTR of MGMT 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. Conclusion: Above all, our findings demonstrate that miR-142-3p plays a critical role in regulating MGMT expression, has great potential for future clinical applications, and acts as a new diagnostic marker for this intractable disease. Keywords: glioblastoma, O6-methylguanine-DNA methyltransferase, miR-142-3p, carmustine, temozolomide |
| first_indexed | 2024-12-17T10:41:57Z |
| format | Article |
| id | doaj.art-3df12c110dcc4bd9985abc4db5bb3a45 |
| institution | Directory Open Access Journal |
| issn | 1179-1322 |
| language | English |
| last_indexed | 2024-12-17T10:41:57Z |
| publishDate | 2018-04-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Cancer Management and Research |
| spelling | doaj.art-3df12c110dcc4bd9985abc4db5bb3a452022-12-21T21:52:13ZengDove Medical PressCancer Management and Research1179-13222018-04-01Volume 1077578537756MicroRNA-142-3p is involved in regulation of MGMT expression in glioblastoma cellsLee YYYarmishyn AAWang MLChen HYChiou SYang YPLin CHuang PIChen YWMa HIChen MYi-Yen Lee,1,2,* Aliaksandr A Yarmishyn,3,4,* Mong-Lien Wang,3,4 Hsiao-Yun Chen,4,5 Shih-Hwa Chiou,3–5 Yi-Ping Yang,4,5 Chun-Fu Lin,1,2 Pin-I Huang,2,6 Yi-Wei Chen,2,6 Hsin-I Ma,7 Ming-Teh Chen1,2 1Department of Neurosurgery, Neurological Institute, Taipei Veterans General Hospital, 2Faculty of Medicine, National Yang-Ming University, 3Institute of Pharmacology, National Yang-Ming University, 4Department of Medical Research, Taipei Veterans General Hospital, 5Institute of Clinical Medicine, National Yang Ming University, 6Cancer Center, Radiation Oncology Division, Taipei Veterans General Hospital, 7Department of Neurological Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan *These authors contributed equally to this work Background: 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 O6 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 O6-methylguanine. Expression levels of MGMT 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. Results: In this study, we sought to investigate whether miR-142-3p can regulate MGMT gene expression in GBM cells. Here, we show that miR-142-3p downregulates MGMT expression through binding to the 3′-UTR of MGMT 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. Conclusion: Above all, our findings demonstrate that miR-142-3p plays a critical role in regulating MGMT expression, has great potential for future clinical applications, and acts as a new diagnostic marker for this intractable disease. Keywords: glioblastoma, O6-methylguanine-DNA methyltransferase, miR-142-3p, carmustine, temozolomidehttps://www.dovepress.com/microrna-142-3p-is-involved-in-regulation-of-mgmt-expression-in-gliobl-peer-reviewed-article-CMARGlioblastoma (GBM)O6-methylguanine-DNA methyltransferase (MGMT)microRNA-142-3p (miR-142-3p)carmustine (BCNU)temozolomide (TMZ). |
| spellingShingle | Lee YY Yarmishyn AA Wang ML Chen HY Chiou S Yang YP Lin C Huang PI Chen YW Ma HI Chen M MicroRNA-142-3p is involved in regulation of MGMT expression in glioblastoma cells Cancer Management and Research Glioblastoma (GBM) O6-methylguanine-DNA methyltransferase (MGMT) microRNA-142-3p (miR-142-3p) carmustine (BCNU) temozolomide (TMZ). |
| title | MicroRNA-142-3p is involved in regulation of MGMT expression in glioblastoma cells |
| title_full | MicroRNA-142-3p is involved in regulation of MGMT expression in glioblastoma cells |
| title_fullStr | MicroRNA-142-3p is involved in regulation of MGMT expression in glioblastoma cells |
| title_full_unstemmed | MicroRNA-142-3p is involved in regulation of MGMT expression in glioblastoma cells |
| title_short | MicroRNA-142-3p is involved in regulation of MGMT expression in glioblastoma cells |
| title_sort | microrna 142 3p is involved in regulation of mgmt expression in glioblastoma cells |
| topic | Glioblastoma (GBM) O6-methylguanine-DNA methyltransferase (MGMT) microRNA-142-3p (miR-142-3p) carmustine (BCNU) temozolomide (TMZ). |
| url | https://www.dovepress.com/microrna-142-3p-is-involved-in-regulation-of-mgmt-expression-in-gliobl-peer-reviewed-article-CMAR |
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