Статья

MicroRNA-214 targets PTK6 to inhibit tumorigenic potential and increase drug sensitivity of prostate cancer cells

Patrice CagleJulius L. Chambers Biomedical Biotechnology Research Institute, North Carolina Central University, Durham, NC, 27707, United StatesSuryakant NitureJulius L. Chambers Biomedical Biotechnology Research Institute, North Carolina Central University, Durham, NC, 27707, United StatesAnvesha SrivastavaCancer Research Laboratory, Division of Science and Mathematics, University of the District of Columbia, Washington, DC, 20008, United StatesMalathi RamalingaCancer Research Laboratory, Division of Science and Mathematics, University of the District of Columbia, Washington, DC, 20008, United StatesRasha AqeelCancer Research Laboratory, Division of Science and Mathematics, University of the District of Columbia, Washington, DC, 20008, United StatesLeslimar Ríos-ColónJulius L. Chambers Biomedical Biotechnology Research Institute, North Carolina Central University, Durham, NC, 27707, United StatesUchechukwu ChimehJulius L. Chambers Biomedical Biotechnology Research Institute, North Carolina Central University, Durham, NC, 27707, United StatesSimeng SuyDepartment of Radiation Medicine, Georgetown University, Washington, DC, 20057, United StatesSean P. CollinsDepartment of Radiation Medicine, Georgetown University, Washington, DC, 20057, United StatesRajvir DahiyaVA Medical Center and University of California San Francisco, San Francisco, CA, 94121, United StatesDeepak KumarCancer Research Laboratory, Division of Science and Mathematics, University of the District of Columbia, Washington, DC, 20008, United States. [email protected]

2019en

ABI

Аннотация

Prostate cancer is the most commonly diagnosed cancer in men with African American men disproportionally suffering from the burden of this disease. Biomarkers that could discriminate indolent from aggressive and drug resistance disease are lacking. MicroRNAs are small non-coding RNAs that affect numerous physiological and pathological processes, including cancer development and have been suggested as biomarkers and therapeutic targets. In the present study, we investigated the role of miR-214 on prostate cancer cell survival/migration/invasion, cell cycle regulation, and apoptosis. miR-214 was differentially expressed between Caucasian and African American prostate cancer cells. Importantly, miR-214 overexpression in prostate cancer cells induced apoptosis, inhibiting cell proliferation and colony forming ability. miR-214 expression in prostate cancer cells also inhibited cell migration and 3D spheroid invasion. Mechanistically, miR-214 inhibited prostate cancer cell proliferation by targeting protein tyrosine kinase 6 (PTK6). Restoration of PTK6 expression attenuated the inhibitory effect of miR-214 on cell proliferation. Moreover, simultaneous inhibition of PTK6 by ibrutinib and miR-214 significantly reduced cell proliferation/survival. Our data indicates that miR-214 could act as a tumor suppressor in prostate cancer and could potentially be utilized as a biomarker and therapeutic target.

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Идентификаторы

DOI: 10.1038/s41598-019-46170-3

Цитирования и источники

Цитирований: 2Использованных источников: 0

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