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Non-Coding RNA 2019, 5(1), 10; https://doi.org/10.3390/ncrna5010010

MicroRNA-4719 and microRNA-6756-5p Correlate with Castration-Resistant Prostate Cancer Progression through Interleukin-24 Regulation

1
Department of Biological Sciences, Herbert H. Lehman College, City University of New York, 250 Bedford Park Boulevard West, Bronx, NY 10468, USA
2
Department of Biology, The Graduate Center, City University of New York, 365 Fifth Avenue, Room 4315, New York, NY 10016, USA
*
Author to whom correspondence should be addressed.
Received: 15 December 2018 / Revised: 16 January 2019 / Accepted: 18 January 2019 / Published: 21 January 2019
(This article belongs to the Special Issue Non-Coding RNA in Reproductive Organ Cancers)
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Abstract

Prostate cancer (PCa) is the second leading cause of cancer death in the United States. The five-year survival rate for men diagnosed with localized PCa is nearly 100%, yet for those diagnosed with aggressive PCa, it is less than 30%. The pleiotropic cytokine Interleukin-24 (IL-24) has been shown to specifically kill PCa cells compared to normal cells when overexpressed in both in vitro and in vivo studies. Despite this, the mechanisms regulating IL-24 in PCa are not well understood. Since specific microRNAs (miRNAs) are dysregulated in PCa, we used miRNA target prediction algorithm tools to identify miR-4719 and miR-6556-5p as putative regulators of IL-24. This study elucidates the expression profile and role of miR-4719 and miR-6756-5p as regulators of IL-24 in PCa. qRT-PCR analysis shows miR-4719 and miR-6756-5p overexpression significantly decreases the expression of IL-24 in PCa cells compared to the negative control. Compared to the indolent PCa and normal prostate epithelial cells, miR-4719 and miR-6756-5p are significantly overexpressed in castration-resistant prostate cancer (CRPC) cell lines, indicating that their gain may be an early event in PCa progression. Moreover, miR-4719 and miR-6756-5p are significantly overexpressed in the CRPC cell line of African-American males (E006AA-hT) compared to CRPC cell lines of Caucasian males (PC-3 and DU-145), indicating that miR-4719 and miR-6756-5p may also play a role in racial disparity. Lastly, the inhibition of expression of miR-4719 and miR-6756-5p significantly increases IL-24 expression and inhibits proliferation and migration of CRPC cell lines. Our findings indicate that miR-4719 and miR-6756-5p may regulate CRPC progression through the targeting of IL-24 expression and may be biomarkers that differentiate between indolent and CRPC. Strategies to inhibit miR-4719 and miR-6756-5p expression to increase IL-24 in PCa may have therapeutic efficacy in aggressive PCa. View Full-Text
Keywords: microRNA; castration-resistant prostate cancer; Interleukin-24; racial disparity microRNA; castration-resistant prostate cancer; Interleukin-24; racial disparity
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Das, D.K.; Persaud, L.; Sauane, M. MicroRNA-4719 and microRNA-6756-5p Correlate with Castration-Resistant Prostate Cancer Progression through Interleukin-24 Regulation. Non-Coding RNA 2019, 5, 10.

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