LncRNA 51325 Alleviates Bone Cancer Induced Hyperalgesia Through Inhibition of Pum2

Abstract

Background

Bone cancer pain (BCP) represents one of the most challenging comorbidities associated with cancer metastasis. Long non-coding RNAs (lncRNAs) have garnered attention as potential therapeutic agents in managing neuropathic pain. However, their role in the regulation of nociceptive information processing remains poorly understood. In this study, we observed a significant down-regulation of the spinal lncRNA ENSRNOG00000051325 (lncRNA51325) in a rat model of bone cancer pain. Our study sought to elucidate the potential involvement of lncRNA51325 in the development of BCP by modulating the expression of molecules associated with pain modulation.

Methods

We established the BCP model by injecting Walker 256 cells into the tibial plateau of rats. We conducted tests on the pain behaviors and anxiety-like responses of rats through von-Frey test, Gait analysis, and Open Field Test. Spinal lumbar expansion was harvested for molecular biology experiments to explore the relationship between lncRNA51325 and Pumilio RNA binding family member 2 (Pum2).

Results

Notably, the overexpression of lncRNA51325 effectively attenuated mechanical allodynia in rats afflicted with BCP, whereas the knockdown of lncRNA51325 induced pain behaviors and anxiety-like responses in naïve rats. Additionally, we observed a time-dependent increase in the expression of Pum2 in BCP-afflicted rats, and intrathecal injection of Pum2-siRNA alleviated hyperalgesia. Furthermore, our investigations revealed that lncRNA51325 exerts a negative modulatory effect on Pum2 expression. The overexpression of lncRNA51325 significantly suppressed Pum2 expression in BCP rats, while the knockdown of lncRNA51325 led to elevated Pum2 protein levels in the spinal cord of naïve rats. Subsequent treatment with Pum2-siRNA mitigated the downregulation of lncRNA51325-induced mechanical allodynia in naïve rats.

Conclusion

Our findings indicate that lncRNA51325 plays a role in regulating bone cancer pain by inhibiting Pum2 expression, offering a promising avenue for novel treatments targeting nociceptive hypersensitivity induced by bone metastatic cancer.

Keywords:

• long non-coding RNA
• bone cancer pain
• Pum2
• spinal cord

Data Sharing Statement

The data used to support the findings of this study are available from the published literature.

Acknowledgments

This work was supported by the China Postdoctoral Science Foundation (2022M712310), the Natural Science Foundation of Zhejiang Province (LGD22H090002, LTGD24H090002), the Medical and Health General Research Program of Zhejiang Province (2021RC130, 2024KY429), the Science and Technology Project of Jiaxing City (2023AY40022, 2023AY11044), the Bengbu Science and Technology Bureau project (20220115), the Key Speciality of Anhui Province (2022-AH-105), the National Clinical Key Specialty Construction Project-Oncology department (2023-GJZK-001), the Zhejiang Provincial Traditional Chinese Medical Innovation Team of China under Grant No. 2022-19, the Key Medical Subjects Established by Zhejiang Province and Jiaxing City Jointly Pain Medicine and Oncology (2019-ssttyx, 2023-SSGJ-001), the Clinical Key Specialty of Zhejiang Province Anesthesiology (2023-ZJZK001) and the Construction Project of Key Laboratory of Nerve and Pain Medicine in Jiaxing City.

Disclosure

The authors report no conflicts of interest in this work.