Oncotarget

Research Papers:

MicroRNA-4287 is a novel tumor suppressor microRNA controlling epithelial-to mesenchymal transition in prostate cancer

Divya Bhagirath, Thao Ly Yang, Theresa Akoto, Nikhil Patel, Laura Z. Tabatabai and Sharanjot Saini _

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Oncotarget. 2020; 11:4681-4692. https://doi.org/10.18632/oncotarget.27849

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Abstract

Divya Bhagirath2, Thao Ly Yang1, Theresa Akoto3, Nikhil Patel4, Laura Z. Tabatabai1 and Sharanjot Saini2

1 Veterans Affairs Medical Center, San Francisco and University of California, San Francisco, CA, USA

2 Department of Biochemistry and Molecular Biology, Augusta University, Augusta, GA, USA

3 Department of Cellular Biology and Anatomy, Augusta University, Augusta, GA, USA

4 Department of Pathology, Augusta University, Augusta, GA, USA

Correspondence to:

Sharanjot Saini,email: ssaini@augusta.edu

Keywords: miR-4287; prostate cancer; chromosome 8p; EMT; SLUG

Received: September 17, 2020     Accepted: December 08, 2020     Published: December 22, 2020

Copyright: © 2020 Bhagirath et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

ABSTRACT

Prostate cancer (PCa) is a significant cause of male morbidity in the United States. Despite recent advances in diagnosis and therapeutic interventions, significant fraction of cases still progress to an advanced stage. Various genetic/epigenetic elements that facilitate this progression are not yet completely known and the mechanism that favors advanced disease is an area of investigation. A characteristic feature associated with progressive disease is deletion of chromosome 8p (chr8p) region, that harbors tumor-suppressor NKX3.1. Previous studies from our group has shown that there are cluster of microRNAs (miRNAs) located within this region whose loss favors advanced, metastatic disease. miR-4287 is a novel miRNA located within this region that has not been studied before. In the present study, we analyzed the role of miR-4287 in PCa using clinical tissues and cell lines. We observed that miR-4287 is significantly downregulated in patient-derived tumor tissues. Receiver operating curve (ROC) analysis showed that miR-4287 distinguishes prostate cancer from normal with a specificity of 88.24% and with an Area under the curve (AUC) of 0.66. Further, we found that miR-4287 levels correlate inversely with patients’ serum prostate-specific antigen levels. Ectopic over-expression of miR-4287 in PCa cell lines showed that miR-4287 plays a tumor suppressor role. miR-4287 led to an increase in G2/M phase of cell cycle in PCa cell lines. Further, ectopic miR-4287 inhibited PCa epithelial-to-mesenchymal transition (EMT) by directly repressing SLUG and stem cell marker CD44. Since miR-4287 specifically targets metastasis pathway mediators, miR-4287 has potential diagnostic and therapeutic significance in preventing advanced, metastatic disease.


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