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Spinal circRNA-9119 Suppresses Nociception by Mediating the miR-26a-TLR3 Axis in a Bone Cancer Pain Mouse Model.

Abstract

Altered expression of circular RNA (circRNA) is recognized as a contributor to malignant pain where microRNA (miRNA) exerts an essential effect. We generated a murine model for bone malignancy pain in which 2472 osteolytic sarcoma cells were injected into the femurs of mice. CircRNA microarray and quantitative PCR (qPCR) and revealed that circ9119 expression was repressed in the spinal cord of bone malignancy pain model mice, which is the first relay site involved in the transmission of nociceptive information to the cerebrum of mice that receive spinal analgesics for malignancy pain. Overexpression of circ9119 by plasmid injection in the model mice reduced progressive thermal hyperalgesia and mechanical hyperalgesia. Bioinformatics prediction and dual-luciferase reporter assay showed that circ9119 functions as a sponge of miR-26a, which targets the TLR3 3'-untranslated region. Furthermore, expression of miR-26a was elevated and TLR3 level was repressed in bone malignancy pain model mice, which were counteracted by circ9119 in the spinal cord of tumor-bearing mice. Moreover, excessive expression of miR-26a was involved in the recovery of mice from progressive thermal hyperalgesia and mechanical hyperalgesia triggered via circ9119. TLR3 knockdown in bone malignancy pain model mice thoroughly impaired pain in the initial stages and reduced the effects of circ9119 on hyperalgesia. Our research findings indicate that targeting the circ9119-miR-26a-TLR3 axis may be a promising analgesic strategy to manage malignancy pain.

Authors+Show Affiliations

Department of Anesthesiology, Shunde Hospital of Southern Medical University, No. 1 Lunjiaojiazi Road, Shunde District, Foshan, 528308, Guangdong, China.Department of Anesthesiology, Shunde Hospital of Southern Medical University, No. 1 Lunjiaojiazi Road, Shunde District, Foshan, 528308, Guangdong, China.Department of Anesthesiology, Shunde Hospital of Southern Medical University, No. 1 Lunjiaojiazi Road, Shunde District, Foshan, 528308, Guangdong, China.Department of Anesthesiology, Shunde Hospital of Southern Medical University, No. 1 Lunjiaojiazi Road, Shunde District, Foshan, 528308, Guangdong, China.Department of Anesthesiology, Shunde Hospital of Southern Medical University, No. 1 Lunjiaojiazi Road, Shunde District, Foshan, 528308, Guangdong, China. zuminxingyx@163.com.Department of Anesthesiology, Shunde Hospital of Southern Medical University, No. 1 Lunjiaojiazi Road, Shunde District, Foshan, 528308, Guangdong, China. ssss047@163.com.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31368062

Citation

Zhang, Zhongqi, et al. "Spinal circRNA-9119 Suppresses Nociception By Mediating the miR-26a-TLR3 Axis in a Bone Cancer Pain Mouse Model." Journal of Molecular Neuroscience : MN, 2019.
Zhang Z, Zhang X, Zhang Y, et al. Spinal circRNA-9119 Suppresses Nociception by Mediating the miR-26a-TLR3 Axis in a Bone Cancer Pain Mouse Model. J Mol Neurosci. 2019.
Zhang, Z., Zhang, X., Zhang, Y., Li, J., Xing, Z., & Zhang, Y. (2019). Spinal circRNA-9119 Suppresses Nociception by Mediating the miR-26a-TLR3 Axis in a Bone Cancer Pain Mouse Model. Journal of Molecular Neuroscience : MN, doi:10.1007/s12031-019-01378-w.
Zhang Z, et al. Spinal circRNA-9119 Suppresses Nociception By Mediating the miR-26a-TLR3 Axis in a Bone Cancer Pain Mouse Model. J Mol Neurosci. 2019 Jul 31; PubMed PMID: 31368062.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Spinal circRNA-9119 Suppresses Nociception by Mediating the miR-26a-TLR3 Axis in a Bone Cancer Pain Mouse Model. AU - Zhang,Zhongqi, AU - Zhang,Xiaoxia, AU - Zhang,Yanjing, AU - Li,Jiyuan, AU - Xing,Zumin, AU - Zhang,Yiwen, Y1 - 2019/07/31/ PY - 2019/03/18/received PY - 2019/07/09/accepted PY - 2019/8/2/entrez KW - Bone cancer pain KW - Circular RNA-9119 KW - Hyperalgesia KW - TLR3 KW - miR-26a JF - Journal of molecular neuroscience : MN JO - J. Mol. Neurosci. N2 - Altered expression of circular RNA (circRNA) is recognized as a contributor to malignant pain where microRNA (miRNA) exerts an essential effect. We generated a murine model for bone malignancy pain in which 2472 osteolytic sarcoma cells were injected into the femurs of mice. CircRNA microarray and quantitative PCR (qPCR) and revealed that circ9119 expression was repressed in the spinal cord of bone malignancy pain model mice, which is the first relay site involved in the transmission of nociceptive information to the cerebrum of mice that receive spinal analgesics for malignancy pain. Overexpression of circ9119 by plasmid injection in the model mice reduced progressive thermal hyperalgesia and mechanical hyperalgesia. Bioinformatics prediction and dual-luciferase reporter assay showed that circ9119 functions as a sponge of miR-26a, which targets the TLR3 3'-untranslated region. Furthermore, expression of miR-26a was elevated and TLR3 level was repressed in bone malignancy pain model mice, which were counteracted by circ9119 in the spinal cord of tumor-bearing mice. Moreover, excessive expression of miR-26a was involved in the recovery of mice from progressive thermal hyperalgesia and mechanical hyperalgesia triggered via circ9119. TLR3 knockdown in bone malignancy pain model mice thoroughly impaired pain in the initial stages and reduced the effects of circ9119 on hyperalgesia. Our research findings indicate that targeting the circ9119-miR-26a-TLR3 axis may be a promising analgesic strategy to manage malignancy pain. SN - 1559-1166 UR - https://www.unboundmedicine.com/medline/citation/31368062/Spinal_circRNA-9119_Suppresses_Nociception_by_Mediating_the_miR-26a-TLR3_Axis_in_a_Bone_Cancer_Pain_Mouse_Model L2 - https://dx.doi.org/10.1007/s12031-019-01378-w DB - PRIME DP - Unbound Medicine ER -