Transcriptomic Analysis of Long Noncoding RNA and mRNA Expression Profiles in the Amygdala of Rats with Bone Cancer Pain-Depression Comorbidity

Wu, Shuyan; Chen, Xiaohui; Huang, Fei; Lin, Mingxue; Chen, Pinzhong; Wan, Haiyang; Gao, Fei; Zheng, Ting; Zheng, Xiaochun

doi:10.3390/life11080834

Cited by 6 publications

(3 citation statements)

References 59 publications

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“…Numerous cancer types, 1 including lung, breast, prostate, thyroid, and kidney cancer, have been identified to exhibit bone metastasis in advanced stages. 2 This metastatic process can lead to adverse consequences, including fractures, 3 pain, hypercalcemia, and compression of the spinal cord and nerves. 4 Notably, bone cancer pain (BCP) is a persistent and intricate form of pain that markedly diminishes a patient's quality of life.…”

Section: Introductionmentioning

confidence: 99%

LncRNA 51325 Alleviates Bone Cancer Induced Hyperalgesia Through Inhibition of Pum2

Wang,

Xu,

Liu

et al. 2024

JPR

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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 downregulation 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 timedependent 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.

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Section: Introductionmentioning

confidence: 99%

LncRNA 51325 Alleviates Bone Cancer Induced Hyperalgesia Through Inhibition of Pum2

Wang,

Xu,

Liu

et al. 2024

JPR

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“…Several causes of bone cancer pain (BCP) have been proposed, including structural reorganization of sensory and sympathetic nerve fibers in the bone, combined with the cellular and neurochemical reorganization in the spinal cord and brain ( Mantyh, 2013 ; Zaja̧czkowska et al, 2019 ). More and more evidence has been accumulated to support the role of central nociceptive hypersensitivity in BCP ( Hou et al, 2020 ; Wu et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Neuroinflammation in the medial prefrontal cortex exerts a crucial role in bone cancer pain

Wang

Zhang

et al. 2022

Front. Mol. Neurosci.

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Bone cancer pain (BCP) is one of the most common types of pain in cancer patients which compromises the patient’s functional status, quality of life, and survival. Central hyperalgesia has increasingly been identified as a crucial factor of BCP, especially in the medial prefrontal cortex (mPFC) which is the main cortical area involved in the process of pain and consequent negative emotion. To explore the genetic changes in the mPFC during BCP occurrence and find possible targets for prediction, we performed transcriptome sequencing of mPFC in the BCP rat model and found a total of 147 differentially expressed mRNAs (DEmRNAs). A protein-protein interaction (PPI) network revealed that the DEmRNAs mainly participate in the inflammatory response. Meanwhile, microglia and astrocytes were activated in the mPFC of BCP rats, further confirming the presence of neuroinflammation. In addition, Gene Ontology (GO) analysis showed that DEmRNAs in the mPFC are mainly involved in antigen processing, presentation of peptide antigen, and immune response, occurring in the MHC protein complex. Besides, the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that DEmRNAs are mainly enriched in the pathways of phagosome, staphylococcus aureus infection, and antigen processing, in which MHCII participate. Furthermore, immunostaining showed that MHCII is mainly located in the microglia. Microglia are believed to be involved in antigen processing, a key cause of BCP. In vivo, minocycline (MC) treatment inhibits the activation of microglia and reduces the expression of MHCII and proinflammatory cytokines, thereby alleviating BCP and pain-related anxiety. Taken together, our study identified differentially expressed genes in the BCP process and demonstrated that the activation of microglia participates in the inflammatory response and antigen process, which may contribute to BCP.

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“…Several causes of bone cancer pain (BCP) have been proposed, including bone destruction and nociceptive hypersensitivity (Mantyh 2013;Zajączkowska et al 2019). Recently, more and more evidence has been accumulated to support the role of central nociceptive hypersensitivity in bone cancer pain (Hou et al 2020; Wu et al 2021).…”

Section: Introductionmentioning

confidence: 99%

MHCII contributes to bone cancer pain via activating the NLRP3 inflammasome in microglia of the medial prefrontal cortex

Wang

Zhang

et al. 2022

Preprint

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As one of the causes of bone cancer pain (BCP), central hyperalgesia has more and more supporting evidence recently. The medial prefrontal cortex (mPFC) is implicated in emotional disorders associated with BCP. Major histocompatibility complex II (MHCII) is a key component in regulating anti-inflammatory response and antigen presentation. This study aims to investigate whether MHCII of the mPFC participates in the BCP. The rat model of BCP was established by injecting Walker 256 cells into the tibia. BCP-induced decreased pain threshold, increased the expression of MHCII and the downstream protein CTSS, CD74 and upstream protein CIITA in mPFC, and the upregulation of MHCII was mainly observed in the mPFC microglia. Furthermore, pharmacological inhibition of MHCII in mPFC by intraperitoneal injecting minocycline provides relief from BCP. Importantly, the upregulation of MHCII is accompanied by significant NLRP3 inflammasome activation and inflammatory factors (IL-1β, IL-18 and TNF-α) released in the mPFC of BCP rats. Taken together, our data suggest that MHCII participates in BCP by activating NLRP3 inflammasome in microglia of the mPFC.

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Transcriptomic Analysis of Long Noncoding RNA and mRNA Expression Profiles in the Amygdala of Rats with Bone Cancer Pain-Depression Comorbidity

Cited by 6 publications

References 59 publications

LncRNA 51325 Alleviates Bone Cancer Induced Hyperalgesia Through Inhibition of Pum2

LncRNA 51325 Alleviates Bone Cancer Induced Hyperalgesia Through Inhibition of Pum2

Neuroinflammation in the medial prefrontal cortex exerts a crucial role in bone cancer pain

MHCII contributes to bone cancer pain via activating the NLRP3 inflammasome in microglia of the medial prefrontal cortex

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