MicroRNA-301a modulates doxorubicin resistance in osteosarcoma cells by targeting AMP-activated protein kinase alpha 1.
MicroRNAs have been implicated in drug resistance of osteosarcoma (OS). MicroRNA-301a (miR-301a) is up-regulated and functions as an oncogene in various cancers. However, little is known about the role of miR-301a in drug resistance of OS cells. In this study, we found that doxorubicin induced time-dependent expression of miR-301a in OS cells. Meantime, doxorubicin promoted HMGCR expression and inhibited AMPKα1 expression, which was further facilitated by miR-301a overexpression. Luciferase reporter assay identified AMPKα1 as direct target gene of miR-301a. Notably, miR-301a reduced doxorubicin-induced cell apoptosis whereas anti-miR-301a enhanced apoptosis in OS cells, suggesting that up-regulation of miR-301a contributed to chemoresistance of OS cells. Consistently, our data showed that miR-301a and HMGCR were up-regulated in chemotherapy-resistant OS compared to those in control OS. Our findings suggested that miR-301a might be a potential biomarker for chemotherapy-resistant OS and a promising therapeutic target for overcoming drug resistance of OS.
Department of Orthopedics, Tianjin Medical University General Hospital, Tianjin 300052, PR China; Department of Joint and Sports Medicine, Affiliated Hospital of Jining Medical College, Jining 272029, PR China.
Yuanmin
Y
Zhang
Department of Joint and Sports Medicine, Affiliated Hospital of Jining Medical College, Jining 272029, PR China.
Guoqing
G
Duan
Department of Orthopedics, Tianjin Medical University General Hospital, Tianjin 300052, PR China. Electronic address: fengsq@hotmail.com.
Shiqing
S
Feng
D055372:AMP-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000235:genetics / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D012516:Osteosarcoma / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
D000970:Antineoplastic Agents; C550735:MIRN301A microRNA, human; D035683:MicroRNAs; D004317:Doxorubicin; C553220:HMGCR protein, human; D006903:Hydroxymethylglutaryl CoA Reductases; D055372:AMP-Activated Protein Kinases; C526180:PRKAA1 protein, human
AMPKα1; Doxorubicin; Drug resistance; HMGCR; MicroRNA-301a; Osteosarcoma