MicroRNA-214 acts as a potential oncogene in breast cancer by targeting the PTEN-PI3K/Akt signaling pathway

Abstract

Breast cancer ranks as the leading cause of cancer-related mortality in females worldwide. It has been proven that microRNAs (miRNAs or miRs), a type of non-coding RNA, are involved in tumorigenesis. An increasing number of studies has confirmed the critical role of miR-214 in certain types of cancer. Nevertheless, the biological function of miR-214, as well as its underlying mechanisms of action in breast cancer remain largely unknown. In the present study, the expression of miR-214 was found to be upregulated in four human breast cancer cell lines in contrast to its expression level in the non-malignant breast epithelial cell line, MCF-10A. Moreover, the overexpression of miR-214 markedly increased cell viability and abrogated the apoptosis triggered by serum starvation, indicating that miR-214 plays a pivotal role in breast cancer cell growth. Further analysis suggested that the upregulation of miR-214 markedly induced the activation of the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway, which largely accounted for the protective effects of miR-124 on cancer cell growth. This was further confimed by pre-treatment with the PI3K/Akt inhibitor, LY294002, which markedly attenuated the miR-214-induced increase in cell viability and resistance to apoptosis. Furthermore, the expression of phosphatase and tensin homolog (PTEN) was decreased following transfection wtih miR-214 mimics and PTEN was confirmed as the direct target of miR-214 by bioinformatics analysis and a dual-firefly luciferase reporter assay. Importantly, the introduction of PTEN cDNA lacking the 3' untranslated region (3'UTR) significantly inhibited the miR-214-induced activation of the PI3K/Akt signaling pathway, and abrogated the protetive effects of miR-214 on cell survival and resistance to apoptosis. Taken together, these findings suggest that miR-214 possesses oncogenic activity and that its effects are mediated through the promotion of cell growth by targeting the PTEN-PI3K/Akt pathway. Thus, pharmaceutical interventions targeting miR-124 may provide a promising therapeutic strategy for the treatment of breast cancer.