miR-23b-5p promotes the chemosensitivity of temozolomide via negatively regulating TLR4 in glioma

Author:

Gao Ke1,Wang Tuo1,Qiao Yuan2,Cui Bo3ORCID

Affiliation:

1. Department of Neurosurgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, China

2. Department of Endocrinology, Shaanxi Provincial People’s Hospital, Xi’an 710068, China

3. Department of Endocrinology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, China

Abstract

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.

Funder

Key Research and Development Program of Shaanxi

National Nature Science Foundation of China

Publisher

China Science Publishing & Media Ltd.

Subject

General Medicine,Biochemistry,Biophysics

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