title: miR-140-5p attenuates chemotherapeutic drug-induced cell death by regulating autophagy through inositol 1,4,5-trisphosphate kinase 2 (IP3k2) in human osteosarcoma cells.
abstract: Acquisition of drug-resistant phenotypes is often associated with chemotherapy in osteosarcoma. A number of studies have demonstrated a critical role for autophagy in osteosarcoma development, therapy and drug resistance. However, the molecular mechanisms underlying the autophagy-mediated chemotherapy resistance of osteosarcoma cells remain largely unknown. In the present study, we determined the autophagy and microRNA-140 (miR-140-5p, miRBase ID: MIMAT0000431) expression induced by chemotherapeutic drugs in osteosarcoma cells. Then we determined the promotory role of miR-140-5p to the chemotherapy-induced autophagy. Our results demonstrated that miR-140-5p expression was highly induced during chemotherapy of osteosarcoma cells, and this was accompanied by up-regulated autophagy. The increased miR-140-5p expression levels up-regulated anticancer drug-induced autophagy in osteosarcoma cells and ameliorated the anticancer drug-induced cell proliferation and viability decrease. Importantly, miR-140-5p regulates this context-specific autophagy through its target, inositol 1,4,5-trisphosphate kinase 2 (IP3k2). Therefore, the results of the present study demonstrated that miR-140-5p mediated drug-resistance in osteosarcoma cells by inducing autophagy. The present study provides evidence of miRNA regulation of autophagy through modulation of IP3 signalling. The present study recognized a novel mechanism of chemoresistance in osteosarcoma cancers.
authors: Department of Orthopaedics, Zhongnan Hospital of Wuhan University, Wuhan 430071, China.
authors: Renxiong
authors: R
authors: Wei
authors: Department of Neurosurgery, Taihe Hospital, Hubei University of Medicine, Shiyan 442000, China.
authors: Gang
authors: G
authors: Cao
authors: Department of Orthopaedics, Zhongnan Hospital of Wuhan University, Wuhan 430071, China.
authors: Zhouming
authors: Z
authors: Deng
authors: Department of Radiology, Hubei Cancer Hospital, Wuhan 430079, China.
authors: Jiajia
authors: J
authors: Su
authors: Department of Orthopaedics, Zhongnan Hospital of Wuhan University, Wuhan 430071, China cailin333@sina.com.
authors: Lin
authors: L
authors: Cai
mesh_terms: D001343:Autophagy / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004317:Doxorubicin / Q000008:administration & dosage; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D012516:Osteosarcoma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics*
chemical_list: D035683:MicroRNAs; C544302:Mirn140 microRNA, human; D004317:Doxorubicin; D017853:Phosphotransferases (Alcohol Group Acceptor); C051038:Inositol 1,4,5-trisphosphate 3-kinase
keywords: 1; 4; 5-trisphosphate (IP3) signalling; autophagy; drug resistance; miRNA-140; osteosarcoma cells