ALKBH5 modulates bone cancer pain in a rat model by suppressing NR2B expression

IF 3.2 4区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biotechnology and applied biochemistry Pub Date : 2024-05-19 DOI:10.1002/bab.2601

Kun Song, Qionghua Cao, Yanping Yang, Yuefen Zuo, Xianping Wu

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引用次数: 0

Abstract

Currently, the clinical treatment of bone cancer pain (BCP) is mainly related to its pathogenesis. The aim of the present study was to elucidate the potential role of N6-methyladenosine (m6A) in BCP in the spinal cord dorsal root ganglia (DRG) of BCP rats and its specific regulatory mechanism in N-methyl-d-aspartate receptor subunit 2B (NR2B). A rat model of BCP was constructed by tibial injection of Walker256 cells, and ALKBH5 and NR2B expression in the spinal cord DRG was detected. ALKBH5 was silenced or overexpressed in PC12 cells to verify the regulatory effect of ALKBH5 on NR2B. The specific mechanism underlying the interaction between ALKBH5 and NR2B was investigated using methylated RNA immunoprecipitation and dual-luciferase reporter gene assays. The results showed increased expression of m6A, decreased expression of ALKBH5, and increased expression of NR2B in the DRG of the BCP rat model. Overexpression of ALKBH5 inhibited NR2B expression, whereas interference with ALKBH5 caused an increase in NR2B expression. In NR2B, interference with ALKBH5 caused an increase in m6A modification, which caused an increase in NR2B. Taken together, ALKBH5 affected the expression of NR2B by influencing the stability of the m6A modification site of central NR2B, revealing that ALKBH5 is a therapeutic target for BCP.

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ALKBH5 通过抑制 NR2B 的表达调节大鼠模型中的骨癌疼痛。

目前，骨癌痛（BCP）的临床治疗主要与其发病机制有关。本研究旨在阐明N6-甲基腺苷（m6A）在BCP大鼠脊髓背根神经节（DRG）BCP中的潜在作用及其在N-甲基-d-天冬氨酸受体亚基2B（NR2B）中的特异性调控机制。通过胫骨注射Walker256细胞构建了BCP大鼠模型，并检测了ALKBH5和NR2B在脊髓DRG中的表达。在PC12细胞中沉默或过表达ALKBH5以验证ALKBH5对NR2B的调控作用。利用甲基化 RNA 免疫沉淀和双荧光素酶报告基因实验研究了 ALKBH5 与 NR2B 相互作用的具体机制。结果显示，在 BCP 大鼠模型的 DRG 中，m6A 的表达增加，ALKBH5 的表达减少，而 NR2B 的表达增加。过表达 ALKBH5 会抑制 NR2B 的表达，而干扰 ALKBH5 则会导致 NR2B 的表达增加。在 NR2B 中，干扰 ALKBH5 会导致 m6A 修饰增加，从而引起 NR2B 的增加。综上所述，ALKBH5通过影响中心NR2B的m6A修饰位点的稳定性来影响NR2B的表达，揭示了ALKBH5是BCP的一个治疗靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Biotechnology and applied biochemistry 工程技术-生化与分子生物学

CiteScore

6.00

自引率

7.10%

发文量

117

审稿时长

3 months

期刊介绍： Published since 1979, Biotechnology and Applied Biochemistry is dedicated to the rapid publication of high quality, significant research at the interface between life sciences and their technological exploitation. The Editors will consider papers for publication based on their novelty and impact as well as their contribution to the advancement of medical biotechnology and industrial biotechnology, covering cutting-edge research in synthetic biology, systems biology, metabolic engineering, bioengineering, biomaterials, biosensing, and nano-biotechnology.