miR-21 confers cisplatin resistance in gastric cancer cells by regulating PTEN

Abstract

Resistance to chemotherapy is a major obstacle for the effective treatment of cancers. The mechanism of chemo-resistance is still poorly understood, however, mounting evidence supports a role for microRNAs (miRNAs) in modulating key cellular pathways mediating response to chemotherapy. microRNA-21 (miR-21) has been implicated in many cancers and contributed to chemo-resistance, but its role in gastric cancer drug resistance still remains unexplored. The aim of this study was to investigate whether miR-21 mediated resistance of the gastric cancer cell line SGC7901 to the chemotherapeutic agent cisplatin (DDP). Our study found that the expression of miR-21 upregulated in the cisplatin resistant cell line SGC7901/DDP compared to its parental line SGC7901. Moreover, over-expression of miR-21 significantly decreased antiproliferative effects and apoptosis induced by cisplatin, while knockdown of miR-21 dramatically increased antiproliferative effects and apoptosis induction by cisplatin. In addition, miR-21 induced cell survival and cisplatin resistance through downregulating the expression of phosphatase and tension homolog deleted on chromosome 10 (PTEN) and activation of Akt pathway. Inhibition of Akt using PI3K inhibitor LY 294002 could abrogate miR-21 induced cell survival. These results suggest that miR-21 may provide a novel mechanism for understanding cisplatin resistance in gastric cancer by modulating PTEN/PI3K/Akt pathway.