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

大蒜素促进过表达 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

  • 影响因子:2.94
  • DOI:10.1007/s12017-020-08592-5
  • 作者列表:"Wu, Henggang","Li, Xu","Zhang, Tiehui","Zhang, Guojun","Chen, Jingnan","Chen, Li","He, Min","Hao, Bilie","Wang, Cheng
  • 发表时间:2020-02-21
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发生化疗耐药的最常见的原发性肿瘤。此前的研究表明,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功能仍不清楚。我们的工作旨在研究潜在的分子机制。结果表明,在大蒜素治疗期间,胶质母细胞瘤中的 miR-486-3p 水平大大增加。过表达 miR-486-3p 增加了体外和体内对替莫唑胺 (TMZ) 的化疗敏感性。O6-methylguanine-DNA 甲基转移酶 (MGMT) 被确定为 miR-486-3p 的直接靶点,miR-486-3p 过表达阻止了 MGMT 的蛋白翻译。此外,过表达 MGMT 可恢复 TMZ 的 miR-486-3p-induced 化疗敏感性。总之,我们的研究表明,大蒜素可以上调胶质母细胞瘤 miR-486-3p,增强 TMZ 的敏感性。结果提示,在未来,大蒜素可作为与 TMZ 的辅助治疗,以改善患者的预后, miR-486-3p 可能成为胶质母细胞瘤治疗的潜在靶点,提高疗效。

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影响因子:3.96
发表时间:2020-01-01
DOI:10.1002/jmri.26786
作者列表:["Bhattacharjee R","Gupta RK","Patir R","Vaishya S","Ahlawat S","Singh A"]

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