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蒜素过表达 miR-486-3p 通过靶向 MGMT 增强胶质母细胞瘤对替莫唑胺的敏感性。

Overexpression miR-486-3p Promoted by Allicin Enhances Temozolomide Sensitivity in Glioblastoma Via Targeting MGMT.

机构信息

Department of Neurosurgery, Wenrong Hospital of Hengdian, Jinhua, 322118, Zhejiang, China.

Department of Neurosurgery, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, 310002, Zhejiang, China.

出版信息

Neuromolecular Med. 2020 Sep;22(3):359-369. doi: 10.1007/s12017-020-08592-5. Epub 2020 Feb 21.

Abstract

Glioblastoma is the most common primary tumor of the central nervous system that develops chemotherapy resistance. Previous studies showed that Allicin could inhibit multiple cancer cells including glioblastoma, but the function of Allicin in glioblastoma is still unclear. Our work aimed to investigate the underlying molecular mechanism. The results showed that miR-486-3p levels were greatly increased in glioblastoma during Allicin treatment. Overexpression of miR-486-3p increased chemosensitivity to temozolomide (TMZ) in vitro and in vivo. O6-methylguanine-DNA methyltransferase (MGMT) was identified as a direct target of miR-486-3p, and miR-486-3p overexpression prevented the protein translation of MGMT. Moreover, overexpression of MGMT restored miR-486-3p-induced chemosensitivity to TMZ. Taken together, our studies revealed that Allicin could upregulate miR-486-3p and enhance TMZ sensitivity in glioblastoma. The results suggested that in the future, Allicin can be used as an adjuvant therapy with TMZ to improve the prognosis of patients, and miR-486-3p may be a potential target for glioblastoma treatment to improve the curative effects.

摘要

胶质母细胞瘤是中枢神经系统最常见的原发性肿瘤,会产生化疗耐药性。先前的研究表明,大蒜素可以抑制包括胶质母细胞瘤在内的多种癌细胞,但大蒜素在胶质母细胞瘤中的作用尚不清楚。我们的工作旨在研究其潜在的分子机制。结果表明,大蒜素处理后胶质母细胞瘤中 miR-486-3p 的水平大大增加。miR-486-3p 的过表达增加了体外和体内对替莫唑胺(TMZ)的化疗敏感性。O6-甲基鸟嘌呤-DNA 甲基转移酶(MGMT)被鉴定为 miR-486-3p 的直接靶标,miR-486-3p 的过表达阻止了 MGMT 的蛋白质翻译。此外,MGMT 的过表达恢复了 miR-486-3p 诱导的 TMZ 化疗敏感性。总之,我们的研究表明,大蒜素可以上调 miR-486-3p 并增强胶质母细胞瘤对 TMZ 的敏感性。结果表明,在未来,大蒜素可以与 TMZ 联合用作辅助治疗,以改善患者的预后,而 miR-486-3p 可能是治疗胶质母细胞瘤以提高疗效的潜在靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d7b/7417398/82cd1e7f1606/12017_2020_8592_Fig1_HTML.jpg

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