MicroRNA-340-5p modulates cisplatin resistance by targeting LPAATβ in osteosarcoma
Rev. bras. pesqui. méd. biol
; Braz. j. med. biol. res;50(5): e6359, 2017. graf
Article
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| LILACS
| ID: biblio-839294
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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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
LILACS
Assunto principal:
Neoplasias Ósseas
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Aciltransferases
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Osteossarcoma
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Cisplatino
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Resistencia a Medicamentos Antineoplásicos
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MicroRNAs
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Antineoplásicos
Limite:
Humans
Idioma:
En
Revista:
Braz. j. med. biol. res
/
Rev. bras. pesqui. méd. biol
Assunto da revista:
BIOLOGIA
/
MEDICINA
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
China
País de publicação:
Brasil