MicroRNA-301a modulates doxorubicin resistance in osteosarcoma cells by targeting AMP-activated protein kinase alpha 1

Biochem Biophys Res Commun. 2015 Apr 10;459(3):367-73. doi: 10.1016/j.bbrc.2015.02.101. Epub 2015 Feb 26.


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.

Keywords: AMPKα1; Doxorubicin; Drug resistance; HMGCR; MicroRNA-301a; Osteosarcoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AMP-Activated Protein Kinases / antagonists & inhibitors*
  • AMP-Activated Protein Kinases / genetics*
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Apoptosis / genetics
  • Bone Neoplasms / drug therapy*
  • Bone Neoplasms / genetics*
  • Bone Neoplasms / metabolism
  • Case-Control Studies
  • Cell Line, Tumor
  • Doxorubicin / pharmacology*
  • Drug Resistance, Neoplasm / genetics
  • Gene Expression Regulation, Enzymologic / drug effects
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Hydroxymethylglutaryl CoA Reductases / genetics
  • Hydroxymethylglutaryl CoA Reductases / metabolism
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Osteosarcoma / drug therapy*
  • Osteosarcoma / genetics*
  • Osteosarcoma / metabolism
  • Up-Regulation / drug effects


  • Antineoplastic Agents
  • MIRN301 microRNA, human
  • MicroRNAs
  • Doxorubicin
  • HMGCR protein, human
  • Hydroxymethylglutaryl CoA Reductases
  • AMP-Activated Protein Kinases
  • PRKAA1 protein, human