MicroRNA-340-5p modulates cisplatin resistance by targeting LPAATβ in osteosarcoma.

Abstract

MicroRNAs (miRNAs) play an important role in drug resistance and modulate the efficiency of chemotherapy. A recent study indicated that miR-340 functions as a tumor suppressor in various types of cancer. However, the role of miR-340 in chemotherapy has not been reported yet. In this study, we found that miR-340 enhanced cisplatin (CDDP)-induced cell death. Induction of miR-340-5p expression decreased the IC50 of CDDP and increased the apoptosis of CDDP-resistant MG-63 and Saos-2 cells. Moreover, miR-340-5p decreased the accumulation of MRP1 and MDR1. We further explored the mechanism underlying the promoting effects of miR-340-5p on CDDP-induced cell death. We identified a potential target of miR-340 in the 3' untranslated region of lysophosphatidic acid acyltransferase (LPAATβ) using the online program Targetscan (http://www.microrna.org). Luciferase reporter assays showed that miR-340 binds to the 3'UTR of LPAATβ. Enforced expression of miR-340-5p decreased the accumulation of LPAATβ in both MG-63 and Saos-2 cells. Silencing LPAATβ decreased the IC50 of CDDP and increased the apoptosis of CDDP-resistant MG-63 and Saos-2 cells, which is consistent with the effect of miR-340-5p on CDDP-induced cell death. Moreover, induced expression of LPAATβ compromised the effects of miR-340-5p on CDDP-induced cell death and accumulation of MRP1 and MDR1. Taken together, our data indicated that miR-340-5p enhanced the sensitivity to CDDP by targeting LPAATβ.

• Authors: L Song, P Duan, Y Gan, P Li, C Zhao, J Xu, Z Zhang, Q Zhou
• Journal: Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas (Braz J Med Biol Res) Vol. 50 Issue 5 Pg. e6359 (Apr 20 2017) ISSN: 1414-431X [Electronic] Brazil
• PMID: 28443990 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• MIRN340 microRNA, human
• MicroRNAs
• Luciferases
• Acyltransferases
• 2-acylglycerophosphate acyltransferase
• Cisplatin

Topics

• Acyltransferases (analysis, drug effects, physiology)
• Antineoplastic Agents (pharmacology)
• Apoptosis (drug effects)
• Blotting, Western
• Bone Neoplasms (drug therapy, physiopathology)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Cisplatin (pharmacology)
• Down-Regulation
• Drug Resistance, Neoplasm (drug effects, physiology)
• Humans
• Luciferases
• MicroRNAs (analysis, drug effects, physiology)
• Osteosarcoma (drug therapy, physiopathology)
• Real-Time Polymerase Chain Reaction