ALKBH5 suppresses miR-29a-3p expression, thereby exacerbating the inflammatory response associated with spinal tuberculosis

Abstract Background N6-methyladenosine (m6A) is the most common and abundant internal modification in RNA. However, the role of m6A in spinal tuberculosis (STB) remains incompletely elucidated. In our previous study, miRNA-seq was performed on peripheral blood and tissues from STB patients, and miR-...

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Main Authors: Mengqi Zhu, Zhengyong Tao, XingYu Duan, Lijun Feng, Xiaojun Ma, Jiong Wang, ZhiYun Shi, Xu Zhang, NingKui Niu
Format: Article
Language:English
Published: BMC 2025-08-01
Series:Journal of Orthopaedic Surgery and Research
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Online Access:https://doi.org/10.1186/s13018-025-06204-1
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Summary:Abstract Background N6-methyladenosine (m6A) is the most common and abundant internal modification in RNA. However, the role of m6A in spinal tuberculosis (STB) remains incompletely elucidated. In our previous study, miRNA-seq was performed on peripheral blood and tissues from STB patients, and miR-29a-3p was identified as differentially expressed in STB patients through screening. In this study, we mainly explored the regulation of miR-29a-3p by ALKB homolog 5 (ALKBH5) in STB. Methods Tissue specimens were obtained from 20 patients with lumbar degenerative disease and 20 patients with STB. The expression levels of ALKBH5 and miR-29a-3p in STB were assessed using qRT-PCR, immunohistochemistry, and immunofluorescence assays. MeRIP analyses were performed to investigate the role of ALKBH5 in regulating the m6A modification of miR-29a-3p. Additionally, Western blot, ELISA, and qRT-PCR techniques were employed to validate the regulatory mechanism of ALKBH5-mediated miR-29a-3p in the inflammatory response associated with STB. Results ALKBH5 was upregulated in both spinal tuberculosis tissues and cellular models, whereas miR-29a-3p exhibited marked downregulation. Inhibition of miR-29a-3p expression led to increased levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-17 A (IL-17 A). Conversely, overexpression of miR-29a-3p effectively suppressed the production of inflammatory factors. Furthermore, ALKBH5 was found to directly target miR-29a-3p and regulate its methylation modification, thereby inhibiting the maturation of miR-29a-3p. Additionally, ALKBH5 suppressed the expression of miR-29a-3p, which in turn promoted the release of inflammatory factors associated with spinal tuberculosis.
ISSN:1749-799X