Tumor suppressor role of microRNA-1296 in triple-negative breast cancer
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Binh Phan1, Shahana Majid2, Sarah Ursu1, David de Semir1, Mehdi Nosrati1, Vladimir Bezrookove1, Mohammed Kashani-Sabet1 and Altaf A. Dar1
1 California Pacific Medical Center Research Institute, San Francisco, CA 94107, USA
2 Department of Urology, Veterans Affairs Medical Center and University of California San Francisco, San Francisco, CA 94121, USA
Altaf A. Dar, email:
Keywords: microRNA-1296, triple negative breast cancer, tumor suppressor, cyclin D1, apoptosis
Received: October 19, 2015 Accepted: January 14, 2016 Published: January 20, 2016
Triple negative breast cancer (TNBC) is an aggressive subtype of breast cancer with a poor prognosis, which lacks effective targeted therapies. There is an urgent need to better understand the underlying molecular mechanisms of TNBC aggressiveness and identify novel, efficient targets for therapeutic intervention.
Methods: miRNA qRT-PCR was used to determine the expression of miR-1296 in cell lines. The miR-1296 overexpression effects in TNBC cell lines were investigated using assays of colony formation, cell cycle and apoptosis. Immunoblotting was performed to determine the expression of the miR-1296 target protein, and luciferase assays were performed to confirm the target of miR-1296 action.
Results: miR-1296 expression was significantly suppressed in TNBC cell lines and tissues samples. Overexpression of miR-1296 significantly suppressed cell proliferation of two TNBC cell lines when compared to control miRNA-expressing cells. A significant decrease in the S-phase of the cell cycle was observed following miR-1296 overexpression, accompanied by induction of apoptosis in TNBC cells. Cyclin D1 (CCND1) was identified as a target of miR-1296 action. miR-1296 overexpression significantly suppressed the luciferase activity of reporter plasmid containing the 3’UTR of CCND1 and protein expression levels of CCND1 in TNBC cells. The effects of miR-1296 overexpression on TNBC cell growth were reversed by CCND1 overexpression. miR-1296 expression sensitized TNBC cells to cisplatin treatment.
Conclusion: Our results demonstrate a novel tumor suppressor role for miR-1296 in triple-negative breast cancer cell lines, identify CCND1 as its target of action, and demonstrate a potential role for miR-1296 in sensitizing breast cancer cells to cisplatin.
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