circStrn3 is involved in bone cancer pain regulation in a rat model

Abstract Bone cancer pain (BCP) is a common chronic pain that is caused by a primary or metastatic bone tumor. More detailed molecular mechanisms of BCP are warranted. In this study, we established a BCP rat model. The von Frey hair test, body weight, and hematoxylin and eosin staining were employed. We screened differentially expressed circRNAs (DECs) between the BCP group and sham group. The results revealed that 850 DECs were significantly up-regulated and 644 DECs were significantly down-regulated in the BCP group. Furthermore, we identified 1177 differentially expressed genes (DEGs) significantly up-regulated and 565 DEGs significantly down-regulated in the BCP group. Gene Ontology annotation of all 1742 DEGs revealed that biological regulation of metabolic processes, cellular processes, and binding were the top enriched terms. For Kyoto Encyclopedia of Genes and Genomes analysis, phagosome, HTLV-I infection, proteoglycans in cancer, and herpes simplex infection were significantly enriched in this study. In addition, we identified four selected circRNAs, chr6:72418120|72430205, chr20:7561057|7573740, chr18:69943105|69944476, and chr5:167516581|167558250, by quantitative real time PCR. chr6:72418120|72430205 (circStrn3) was selected for further study based on expression level and the circRNA–miRNA–mRNA network table. Western blot analysis suggested that knockdown of circStrn3 could effectively induce Walker 256 cell apoptosis. In summary, our study provided a more in-depth understanding of the molecular mechanisms of BCP.

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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

Life ◽

10.3390/life11080834 ◽

2021 ◽

Vol 11 (8) ◽

pp. 834

Author(s):

Shuyan Wu ◽

Xiaohui Chen ◽

Fengyi Huang ◽

Mingxue Lin ◽

Pinzhong Chen ◽

...

Keyword(s):

Cancer Pain ◽

Noncoding Rna ◽

Molecular Mechanisms ◽

Expression Profiles ◽

Therapeutic Targets ◽

Bone Cancer ◽

Clinical Problem ◽

Differentially Expressed ◽

Bone Cancer Pain ◽

Protein Protein Interaction

Bone cancer pain (BCP)–depression comorbidity has become a complex clinical problem during cancer treatment; however, its underlying molecular mechanisms have not been clarified. Several long noncoding RNAs (lncRNAs) have been demonstrated to be promising therapeutic targets in depression, but research on the role of lncRNAs in BCP–depression comorbidity has been limited. Therefore, high-throughput RNA sequencing was performed to detect differentially expressed profiles in the amygdala of a BCP–depression rat model in this study. We detected 330 differentially expressed mRNAs (DEmRNAs) and 78 differentially expressed lncRNAs (DElncRNAs) in the BCP–depression comorbidity model and then verified the expression of six DEmRNAs and six DElncRNAs with the greatest degrees of difference by RT-qPCR. Furthermore, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed that differentially expressed genes were strongly enriched in inflammatory and immunologic systemic responses. Then the nuclear factor kappa B (NF-κB) signaling pathway and the Th17 differentiation pathway showed significant differences, as determined by Western blot analysis. Finally, we constructed a protein–protein interaction (PPI) network to explore the potential regulatory mechanism of DEmRNAs. In conclusion, our study reveals a new resource for the understanding of dysregulated lncRNAs and mRNAs in BCP–depression comorbidity and provides novel potential therapeutic targets for further approaches.

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The circular RNA circSlc7a11 promotes bone cancer pain pathogenesis in rats by modulating LLC-WRC 256 cell proliferation and apoptosis

Molecular and Cellular Biochemistry ◽

10.1007/s11010-020-04020-1 ◽

2021 ◽

Author(s):

Han-Wen Chen ◽

Xiao-Xia Zhang ◽

Zhu-Ding Peng ◽

Zu-Min Xing ◽

Yi-Wen Zhang ◽

...

Keyword(s):

Cell Proliferation ◽

Cancer Pain ◽

Expression Profiles ◽

Bone Cancer ◽

Circular Rna ◽

Differentially Expressed ◽

Bone Cancer Pain ◽

Circular Rnas ◽

Altered Expression ◽

Proliferation And Apoptosis

AbstractTreatment of bone cancer pain (BCP) caused by bone metastasis in advanced cancers remains a challenge in clinical oncology, and the underlying mechanisms of BCP are poorly understood. This study aimed to investigate the pathogenic roles of circular RNAs (circRNAs) in regulating cancer cell proliferation and BCP development. Eight differentially expressed circRNAs in the rat spinal cord were validated by agarose gel electrophoresis and Sanger sequencing. Expression of circRNAs and mRNAs was detected by quantitative RT-PCR. MTS assay and flow cytometry were performed to analyze cell proliferation and apoptosis, respectively. Differentially expressed mRNA profiles were characterized by deep RNA sequencing, hierarchical clustering, and functional categorization. The interactions among circRNAs, microRNAs (miRNAs), and mRNAs were predicted using TargetScan. Additionally, western blot was performed to determine the protein levels of Pax8, Isg15, and Cxcl10. Multiple circRNAs were differentially expressed in the spinal cords of BCP model rats; of these, circSlc7a11 showed the greatest increase in expression. The overexpression of circSlc7a11 significantly promoted cell proliferation and repressed apoptosis of LLC-WRC 256 and UMR-106 cells, whereas circSlc7a11 silencing produced the opposite effects. Altered expression of circSlc7a11 also induced substantial changes in the mRNA expression profiles of LLC-WRC 256 cells; these changes were linked to multiple apoptotic processes and signaling pathways, such as the chemokine signaling pathway, and formed a complex circRNA/miRNA/mRNA network. Additionally, Pax8, Isg15, and Cxc110 protein level in LLC-WRC 256 cells was consistent with the mRNA results. The circRNA circSlc7a11 regulates rat BCP development by modulating LLC-WRC 256 cell proliferation and apoptosis through multiple-signaling mechanisms.

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Activation of spinal microglia and astrocytes in a rat model of bone cancer pain

Neuroscience Research ◽

10.1016/j.neures.2009.09.947 ◽

2009 ◽

Vol 65 ◽

pp. S178

Author(s):

Yan-Qing Wang ◽

Qi-Liang Mao-Ying ◽

Xiao-Wei Wang ◽

Gen-Cheng Wu

Keyword(s):

Cancer Pain ◽

Rat Model ◽

Bone Cancer ◽

Bone Cancer Pain

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Protease-Activated Receptor 2 Antagonist Potentiates Analgesic Effects of Systemic Morphine in a Rat Model of Bone Cancer Pain

Regional Anesthesia and Pain Medicine ◽

10.1097/aap.0000000000000211 ◽

2015 ◽

Vol 40 (2) ◽

pp. 158-165 ◽

Cited By ~ 5

Author(s):

Yanju Bao ◽

Wei Hou ◽

Liping Yang ◽

Xiangying Kong ◽

Maobo Du ◽

...

Keyword(s):

Cancer Pain ◽

Rat Model ◽

Bone Cancer ◽

Bone Cancer Pain ◽

Analgesic Effects ◽

Protease Activated Receptor 2

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Antinociceptive Effect of Intrathecal Injection of Genetically Engineered Human Bone Marrow Stem Cells Expressing the Human Proenkephalin Gene in a Rat Model of Bone Cancer Pain

Pain Research and Management ◽

10.1155/2017/7346103 ◽

2017 ◽

Vol 2017 ◽

pp. 1-11 ◽

Cited By ~ 4

Author(s):

Yi Sun ◽

Yuke Tian ◽

Haifeng Li ◽

Dengwen Zhang ◽

Qiang Sun

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Gene Transfer ◽

Cancer Pain ◽

Rat Model ◽

Bone Cancer ◽

Genetically Engineered ◽

Human Bone ◽

Human Bone Marrow ◽

Bone Cancer Pain

Background. This study aimed to investigate the use of human bone marrow mesenchymal stem cells (hBMSCs) genetically engineered with the human proenkephalin (hPPE) gene to treat bone cancer pain (BCP) in a rat model.Methods. Primary cultured hBMSCs were passaged and modified with hPPE, and the cell suspensions (6 × 106) were then intrathecally injected into a rat model of BCP. Paw mechanical withdrawal threshold (PMWT) was measured before and after BCP. The effects of hPPE gene transfer on hBMSC bioactivity were analyzed in vitro and in vivo.Results. No changes were observed in the surface phenotypes and differentiation of hBMSCs after gene transfer. The hPPE-hBMSC group showed improved PMWT values on the ipsilateral side of rats with BCP from day 12 postoperatively, and the analgesic effect was reversed by naloxone. The levels of proinflammatory cytokines such as IL-1βand IL-6 were ameliorated, and leucine-enkephalin (L-EK) secretion was augmented, in the hPPE-engineered hBMSC group.Conclusion. The intrathecal administration of BMSCs modified with the hPPE gene can effectively relieve pain caused by bone cancer in rats and might be a potentially therapeutic tool for cancer-related pain in humans.

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Spinal glial activation in a new rat model of bone cancer pain produced by prostate cancer cell inoculation of the tibia

Pain ◽

10.1016/j.pain.2005.08.001 ◽

2005 ◽

Vol 118 (1) ◽

pp. 125-136 ◽

Cited By ~ 138

Author(s):

Rui-Xin Zhang ◽

Bing Liu ◽

Linbo Wang ◽

Ke Ren ◽

Jian-Tian Qiao ◽

...

Keyword(s):

Prostate Cancer ◽

Cancer Pain ◽

Cancer Cell ◽

Rat Model ◽

Prostate Cancer Cell ◽

Bone Cancer ◽

Glial Activation ◽

Bone Cancer Pain ◽

Cell Inoculation

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Behavioral, Medical Imaging and Histopathological Features of a New Rat Model of Bone Cancer Pain

PLoS ONE ◽

10.1371/journal.pone.0013774 ◽

2010 ◽

Vol 5 (10) ◽

pp. e13774 ◽

Cited By ~ 35

Author(s):

Louis Doré-Savard ◽

Valérie Otis ◽

Karine Belleville ◽

Myriam Lemire ◽

Mélanie Archambault ◽

...

Keyword(s):

Medical Imaging ◽

Cancer Pain ◽

Rat Model ◽

Bone Cancer ◽

Bone Cancer Pain ◽

Histopathological Features

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Preconditioning with hydrogen sulfide prevents bone cancer pain in rats through a proliferator-activated receptor gamma/p38/Jun N-terminal kinase pathway

Experimental Biology and Medicine ◽

10.1177/1535370217740859 ◽

2017 ◽

Vol 243 (1) ◽

pp. 57-65 ◽

Cited By ~ 3

Author(s):

Li Zhuang ◽

Ke Li ◽

Gaowei Wang ◽

Tao Shou ◽

Chunlin Gao ◽

...

Keyword(s):

Spinal Cord ◽

Cancer Pain ◽

Rat Model ◽

Mechanical Allodynia ◽

Antinociceptive Effect ◽

Thermal Hyperalgesia ◽

Bone Cancer ◽

Bone Cancer Pain ◽

Kinase Pathway

Bone cancer pain (BCP) is a severe type of hyperpathic pain occurring with primary bone tumors or advanced cancers which metastasize to bones. BCP can detrimentally reduce quality of life and presents a challenge to modern medicine. Studies have shown that exogenous H2S may act as a neuroprotectant to protect against some diseases in central nervous system. The preset study aimed to investigate the antinociceptive effect of H2S in BCP. We first measured the changes of serum H2S in patients with BCP and analyzed the relationship between them, then investigated the effect of H2S preconditioning on BCP, and explored the mechanism in rat model. Our results revealed that serum H2S level was negatively correlated with pain scores. In the rat model of BCP, preconditioning with H2S significantly reduced BCP, demonstrated by the decrease of thermal hyperalgesia and mechanical allodynia. The mechanism of H2S preconditioning may involve microglia deactivation and inflammation inhibition in the spinal cord, in which the proliferator-activated receptor gamma/p38/Jun N-terminal kinase pathway is activated. Impact statement Bone cancer pain (BCP) significantly decreases the life quality of patients or their life expectancy and causes a severe health burden to the society. However, as the exact mechanism of BCP is still poorly understood, no effective treatment has been developed yet. There are some pain medicines now, but they have some inevitable side effects. Additional therapeutic strategies are urgently needed. First, we revealed that preconditioning with H2S significantly reduced BCP, demonstrated by the decrease of thermal hyperalgesia and mechanical allodynia. Second, the mechanism of H2S preconditioning was elucidated. It may involve microglia deactivation and inflammation inhibition in the spinal cord, in which the proliferator-activated receptor gamma/p38/Jun N-terminal kinase pathway is activated. This novel finding may significantly help us to understand the difference between the roles of endogenous H2S and exogenous H2S in the development of BCP and present us a new strategy of pain management.

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