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

Autor: Lei Song, Ping Duan, Pei Li, Yibo Gan, Jia Xu, Zetong Zhang, Chen Zhao, Qiang Zhou
Rok vydání: 2017
Předmět:
0301 basic medicine
Physiology
LPAATβ
Apoptosis
Biochemistry
0302 clinical medicine
General Pharmacology
Toxicology and Pharmaceutics
Luciferases
miR-340-5p
lcsh:QH301-705.5
lcsh:R5-920
Osteosarcoma
General Neuroscience
General Medicine
030220 oncology & carcinogenesis
lcsh:Medicine (General)
medicine.drug
inorganic chemicals
Programmed cell death
Sensitivity to cisplatin
Immunology
Blotting
Western
Biophysics
Down-Regulation
Ocean Engineering
Antineoplastic Agents
Bone Neoplasms
Biology
Real-Time Polymerase Chain Reaction
03 medical and health sciences
Downregulation and upregulation
Cell Line
Tumor
microRNA
medicine
Gene silencing
Humans
neoplasms
Cell Proliferation
Cisplatin
Cell growth
Biomedical Sciences
Cell Biology
Molecular biology
MicroRNAs
030104 developmental biology
lcsh:Biology (General)
Cell culture
Drug Resistance
Neoplasm
Cancer research
Acyltransferases
Zdroj: Brazilian Journal of Medical and Biological Research
Brazilian Journal of Medical and Biological Research, Vol 50, Iss 5
ISSN: 1414-431X
Popis: 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.
Databáze: OpenAIRE
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