MicroRNA-1254 exerts oncogenic effects by directly targeting RASSF9 in human breast cancer

Li,Bin; Chen,Peng; Wang,Jialin; Wang,Linxia; Ren,Mingzhi; Zhang,Ruisan; He,Jianjun

doi:10.3892/ijo.2018.4530

MicroRNA-1254 exerts oncogenic effects by directly targeting RASSF9 in human breast cancer

Authors:
- Bin Li
- Peng Chen
- Jialin Wang
- Linxia Wang
- Mingzhi Ren
- Ruisan Zhang
- Jianjun He
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Affiliations: Department of Breast Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China, Institution of Basic Medical Science, Xi'an Medical University, Xi'an, Shaanxi 710021, P.R. China, Affiliated Baoji Hospital of Xi'an Medical University, Baoji, Shaanxi 721006, P.R. China, Foreign Language College, Xi'an Technological University, Xi'an, Shaanxi 710059, P.R. China, Affiliated Baoji Hospital of Xi'an Medical University, Baoji, Shaanxi 721006, P.R. China, Department of Breast Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China
Published online on: August 21, 2018 https://doi.org/10.3892/ijo.2018.4530
Pages: 2145-2156

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Abstract

MicroRNAs (miRNAs or miRs) play crucial roles in human breast cancer. Although miR-1254 has been shown to have oncogenic activity in several cancer types, its biological function in breast cancer and its mechanisms of action remain unclear. In this study, we investigated the role of miR-1254 in human breast cancer and sought to elucidate the relevant underlying mechanisms. We found that miR-1254 expression was markedly increased in breast cancer tissues and cell lines. Additionally, miR-1254 overexpression accelerated breast cancer cell proliferation, cell cycle G1-S phase transition and inhibited apoptosis. Nevertheless, the inhibition of miR-1254 suppressed cell proliferation and induced apoptosis. Further analyses revealed that miR-1254 expression negatively correlated with RASSF9 expression in breast cancer tissues. We verified that RASSF9 was a direct target of miR-1254 using a luciferase reporter assay. The overexpression of miR-1254 reduced the RASSF9 mRNA and protein levels, and the suppression of miR-1254 promoted RASSF9 expression. Notably, the knockdown or overexpression of RASSF9 corroborated the biological effects observed upon miR-1254 overexpression or inhibition. Taken together, these results demonstrate that miR-1254 accelerates breast cancer cell growth by activating the AKT signaling pathway and suppresses apoptosis by inhibiting p53 expression through the targeting of RASSF9. The data indicate that miR-1254 plays a crucial role in human breast cancer, and may represent a novel therapeutic target for this malignancy.

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