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Published on: October 6, 2022
ALKBH5 modulates bone cancer pain in a rat model by suppressing NR2B expression
Kun Song1,2, Qionghua Cao3, Yanping Yang1,2
1Department of Anesthesiology, Shunde Hospital of Guangzhou University of Chinese Medicine, Foshan, China.
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.
Insights
N6-methyladenosine (m6A) modification and ALKBH5 regulate bone cancer pain (BCP) by affecting N-methyl-d-aspartate receptor subunit 2B (NR2B) stability in dorsal root ganglia. ALKBH5 emerges as a potential therapeutic target for BCP.
Area of Science:
- Molecular Biology
- Neuroscience
- Oncology
Background:
- Clinical treatments for bone cancer pain (BCP) often target its underlying pathogenesis.
- N6-methyladenosine (m6A) is a crucial epitranscriptomic modification involved in various biological processes.
Purpose of the Study:
- To investigate the role of m6A modification in BCP within the spinal cord dorsal root ganglia (DRG).
- To elucidate the regulatory mechanism of ALKBH5 on N-methyl-d-aspartate receptor subunit 2B (NR2B) in the context of BCP.
Main Methods:
- A rat model of BCP was established using Walker256 cell injection.
- ALKBH5 expression was manipulated (silenced/overexpressed) in PC12 cells.
- Mechanisms were explored using methylated RNA immunoprecipitation and dual-luciferase reporter assays.
Main Results:
- BCP rats exhibited increased m6A levels, decreased ALKBH5, and elevated NR2B expression in DRG.
- ALKBH5 overexpression reduced NR2B expression; ALKBH5 interference increased NR2B expression.
- ALKBH5 influences NR2B expression stability via m6A modification.
Conclusions:
- ALKBH5 plays a significant role in BCP by modulating NR2B expression through m6A modification.
- ALKBH5 represents a promising therapeutic target for managing bone cancer pain.
