title: Effects ofmiR-338on morphine tolerance by targeting CXCR4 in a rat model of bone cancer pain.
abstract: The present study aimed to investigate the effects ofmiR-338on morphine tolerance through the targeting of CXC chemokine receptor-4 (CXCR4) in a rat model of bone cancer pain (BCP). Sprague-Dawley (SD) rats were obtained and divided into model saline (n=10), model morphine (n=50), normal saline (n=10) and normal morphine (healthy rats,n=10) groups. After BCP rat model establishment, the remaining SD rats (n=40) in the model saline group were assigned into pLV-THM-miR-338, pLV-THM-anti-miR-338, CXCR4 shRNA, blank and PBS groups. Luciferase reporter gene assay was used for luciferase activity. Quantitative real-time PCR (qRT-PCR) and Western blotting were performed to detect themiR-338and CXCR4 mRNA and protein expression. The model saline group showed increased mRNA and protein expressions of CXCR4 but decreasedmiR-338compared with the model saline group, and the model morphine group had increased mRNA and protein expressions of CXCR4 but decreasedmiR-338compared with the model saline group. The mRNA and protein expressions ofmiR-338in the pLV-THM-miR-338group increased remarkably while those of the pLV-THM-anti-miR-338group decreased significantly compared with the CXCR4 shRNA, blank and PBS groups. The pLV-THM-miR-338, pLV-THM-anti-miR-338, CXCR4 shRNA and CXCR4 mRNA groups all had lower mRNA and protein expressions of CXCR4 than those in the blank and PBS groups.miR-338exerts significant influence in the inhibition of morphine tolerance by suppressing CXCR4 in BCP.
authors.affiliation: Department of Anesthesiology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, P.R. China.
authors.forename: Hong-Xia
authors.initials: HX
authors.lastname: Mei
authors.affiliation: Department of Pain Management, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, P.R. China.
authors.forename: Min-Hong
authors.initials: MH
authors.lastname: Zhou
authors.affiliation: Department of Pharmaceutics, The Pharmacy College of Jinan University, Guangzhou 510632, P.R. China.
authors.forename: Xing-Wang
authors.initials: XW
authors.lastname: Zhang
authors.affiliation: Department of Pain Management, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, P.R. China.
authors.forename: Xi-Xi
authors.initials: XX
authors.lastname: Huang
authors.affiliation: Department of Orthopedics, Wenzhou Province Hospital of TCM, Wenzhou 325027, P.R. China.
authors.forename: Yong-Le
authors.initials: YL
authors.lastname: Wang
authors.affiliation: Department of Pain Management, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, P.R. China.
authors.forename: Pei-Fang
authors.initials: PF
authors.lastname: Wang
authors.affiliation: Department of Pain Management, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, P.R. China mrzhangh34@163.com.
authors.forename: Gong-Hao
authors.initials: GH
authors.lastname: Zhan
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D015153:Blotting, Western; D001859:Bone Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D000072716:Cancer Pain / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D004195:Disease Models, Animal; D004361:Drug Tolerance / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D035683:MicroRNAs / Q000235:genetics*; D008856:Microscopy, Fluorescence; D009020:Morphine / Q000494:pharmacology*; D034622:RNA Interference; D017207:Rats, Sprague-Dawley; D019718:Receptors, CXCR4 / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: C486264:Cxcr4 protein, rat; C573089:MIRN338 microRNA, rat; D035683:MicroRNAs; D019718:Receptors, CXCR4; D009020:Morphine
keywords: CXCR4; MiR-338; PLV-THM-miR-338 lentivirus; PNL-RiCXCR4 lentivirus; bone cancer pain; morphine tolerance