Abstract

Glioma is the most common malignancy in the brain, with poor survival and often highly resistant to chemotherapy and radiotherapy. Temozolomide (TMZ) is an alkylating agent widely used for glioma treatment. However, resistance to TMZ results in treatment failure, while the underlying mechanisms remain unclear. Mounting evidence suggests that dysregulated microRNA (miRNA) expression plays a critical function in glioma development and resistance to TMZ treatment. In this study, we found that miR-23b-5p was downregulated in glioma tissues and cell lines. Overexpression of miR-23b-5p inhibited cell proliferation and promoted cell apoptosis in glioma cells, while miR-23b-5p enhanced the chemosensitivity of TMZ in glioma cells. Furthermore, we identified that Toll-like receptor 4 (TLR4) is a direct target of miR-23b-5p in glioma cells. Knockdown of TLR4 suppressed cell proliferation and enhanced cell apoptosis and promoted chemosensitivity to TMZ treatment in glioma cells. In addition, we demonstrated that overexpression of TLR4 abrogated the regulatory function of miR-23b-5p in glioma cells on cell proliferation, cell apoptosis, and the chemosensitivity of TMZ treatment. In summary, our data suggest that miR-23b-5p promotes the chemosensitivity of TMZ via negatively regulating TLR4 in glioma, which provides a new therapeutic strategy for TMZ-resistant glioma treatment.

中文翻译：

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miR-23b-5p通过负调节胶质瘤TLR4促进替莫唑胺的化疗敏感性

摘要

神经胶质瘤是大脑中最常见的恶性肿瘤，生存率低，并且通常对化疗和放疗具有很强的抵抗力。替莫唑胺 (TMZ) 是一种广泛用于胶质瘤治疗的烷化剂。然而，对 TMZ 的耐药性会导致治疗失败，而其潜在机制仍不清楚。越来越多的证据表明，失调的 microRNA (miRNA) 表达在胶质瘤的发展和对 TMZ 治疗的抵抗中起着关键作用。在这项研究中，我们发现 miR-23b-5p 在神经胶质瘤组织和细胞系中下调。miR-23b-5p的过表达抑制了胶质瘤细胞的细胞增殖并促进了细胞凋亡，而miR-23b-5p增强了胶质瘤细胞中TMZ的化学敏感性。此外，我们发现 Toll 样受体 4 (TLR4) 是神经胶质瘤细胞中 miR-23b-5p 的直接靶标。敲除 TLR4 可抑制细胞增殖并增强细胞凋亡，并促进胶质瘤细胞对 TMZ 治疗的化学敏感性。此外，我们证明 TLR4 的过表达消除了胶质瘤细胞中 miR-23b-5p 对细胞增殖、细胞凋亡和 TMZ 治疗的化学敏感性的调节功能。总之，我们的数据表明 miR-23b-5p 通过负调节胶质瘤中的 TLR4 来促进 TMZ 的化学敏感性，这为 TMZ 耐药的胶质瘤治疗提供了新的治疗策略。和 TMZ 治疗的化学敏感性。总之，我们的数据表明 miR-23b-5p 通过负调节胶质瘤中的 TLR4 来促进 TMZ 的化学敏感性，这为 TMZ 耐药的胶质瘤治疗提供了新的治疗策略。和 TMZ 治疗的化学敏感性。总之，我们的数据表明 miR-23b-5p 通过负调节胶质瘤中的 TLR4 来促进 TMZ 的化学敏感性，这为 TMZ 耐药的胶质瘤治疗提供了新的治疗策略。