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- Title
miR-1197抑制MGMT表达对胶质瘤替莫唑胺耐药性的影响.
- Authors
聂耳; 石秦宇; 韩正中; 张旭; 苗发安
- Abstract
Objective To investigate whether miR-11 97 modulates temozolomide ( TMZ) resistance in glioblastoma via reducing the expression of 0 6 -methylguanine-DNA methyltransferase ( MGMT) . Methods The RNA levels of miR-1197 in glioblastoma ( GBM) and non-tumor brain tissues were determine by quantitative real-time PCR( qRT-PCR) . Cell proliferation was measured by CCK-8 and colony formation assay. Flow cytometry was used to detected cells apoptosis rates. The expression of MGMT was detected by Western blot and qRT-PCR. Luciferase reporter assay was used to investigate the correlation of miR-1197 and MGMT. Subcutaneous xenograft tumor model were used to determine the function of miR-1197 in temozolomide-resistance. Results The biomedical databases and GBM tissue samples analysis showed that miR-1197 expression levels were significantly decreased in GBM. Luciferase reporter assay indicated that miR-1197 directly targets MGMT by binding its seed region to the 3'-UTR of MGMT. And miR-1197 overexpression decreased the protein and RNA levels of MGMT. The combination treatment of miR-1197 plus TMZ significantly induced cell apoptosis, whereas forced expression of MGMT partially abolished this effect. miR-1197 overexpression enhanced temozolomide-induced growth inhibition in vivo. Conclusion miR-1197 enhances TMZ sensitivity through binding to the 3'-UTR of MGMT and repressing MGMT expression.
- Publication
Journal of Clinical Neurosurgery / Linchuang Shenjingwaike Zazhi, 2020, Vol 17, Issue 6, p645
- ISSN
1672-7770
- Publication type
Article
- DOI
10.3969/j.issn.1672-7770.2020.06.010