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

Wang,Fang; Li,Lin; Chen,Zhuo; Zhu,Mingzhi; Gu,Yuanting

doi:10.3892/ijmm.2016.2518

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

Authors:
- Fang Wang
- Lin Li
- Zhuo Chen
- Mingzhi Zhu
- Yuanting Gu
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Affiliations: The Second Department of Breast Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China
Published online on: March 7, 2016 https://doi.org/10.3892/ijmm.2016.2518
Pages: 1421-1428

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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.

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