| MiR-21 protected human glioblastoma U87MG cells from chemotherapeutic drug temozolomide induced apoptosis by decreasing Bax/Bcl-2 ratio and caspase-3 activity. | |
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MedLine Citation:
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PMID: 20633539 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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MicroRNAs (miRNAs) are small noncoding RNA molecules that regulate protein expression by cleaving or repressing the translation of target mRNAs. In mammal animals, their function mainly represses the target mRNAs transcripts via imperfectly complementary to the 3'UTR of target mRNAs. Several miRNAs have been recently reported to be involved in modulation of glioma development, especially some up-regulated miRNAs, such as microRNA-21 (miR-21), which has been found to function as an oncogene in cultured glioblastoma multiforme cells. Temozolomide (TMZ), an alkylating agent, is a promising chemotherapeutic agent for treating glioblastoma. However, resistance develops quickly and with high frequency. To explore the mechanism of resistance, we found that miR-21 could protect human glioblastoma U87MG cells from TMZ induced apoptosis. Our studies showed that TMZ markedly enhanced apoptosis in U87MG cells compared with untreated cells (P<0.05). However, over-express miR-21 in U87MG cells could significantly reduce TMZ-induced apoptosis (P<0.05). Pro-apoptotic Bax and anti-apoptotic Bcl-2 proteins are known to regulate the apoptosis of glioma cells. Bcl-2, resistance to induction of apoptosis, constitutes one major obstacle to chemotherapy in many cancer cells. Bax is shown to correlate with an increased survival of glioblastoma multiforme patients. Further research demonstrated that the mechanism was associated with a shift in Bax/Bcl-2 ratio and change in caspase-3 activity. Compared to control cells, cells treated with TMZ showed a significant increase in the Bax/Bcl-2 ratio and caspase-3 activity (P<0.01). However, such effect was partly prevented by treatment of cells with miR-21 overexpression before, which appeared to downregulate the Bax expression, upregulate the Bcl-2 expression and decrease caspase-3 activity. Taken together, these results suggested that over-express miR-21 could inhibit TMZ-induced apoptosis in U87MG cells, at least in part, by decreasing Bax/Bcl-2 ratio and caspase-3 activity, which highlighted the possibility of miR-21 overexpression in the clinical resistance to chemotherapeutic therapy of TMZ. |
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Authors:
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Lei Shi; Jian Chen; Jian Yang; Tianhong Pan; Shuguang Zhang; Zhimin Wang |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-07-13 |
Journal Detail:
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Title: Brain research Volume: 1352 ISSN: 1872-6240 ISO Abbreviation: Brain Res. Publication Date: 2010 Sep |
Date Detail:
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Created Date: 2010-08-23 Completed Date: 2010-12-22 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0045503 Medline TA: Brain Res Country: Netherlands |
Other Details:
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Languages: eng Pagination: 255-64 Citation Subset: IM |
Affiliation:
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Department of Neurosurgery, The First People's Hospital of Kunshan affiliated with Jiangsu University, Suzhou, PR China. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Antineoplastic Agents, Alkylating
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pharmacology* Apoptosis / drug effects* Brain Neoplasms / drug therapy Caspase 3 / drug effects, metabolism* Cell Division / drug effects Cell Line, Tumor Dacarbazine / analogs & derivatives*, pharmacology Flow Cytometry Glioblastoma / drug therapy, pathology* Glioma / drug therapy Humans MicroRNAs / genetics, pharmacology*, therapeutic use Proto-Oncogene Proteins c-bcl-2 / drug effects, metabolism* bcl-2-Associated X Protein / drug effects, metabolism* |
| Chemical | |
Reg. No./Substance:
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0/Antineoplastic Agents, Alkylating; 0/MIRN21 microRNA, human; 0/MicroRNAs; 0/Proto-Oncogene Proteins c-bcl-2; 0/bcl-2-Associated X Protein; 4342-03-4/Dacarbazine; 85622-93-1/temozolomide; EC 3.4.22.-/Caspase 3 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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