Abstract Deletion of chromosome (chr)8p21-22 region that has been traditionally associated with the loss of homeodomain protein, NKX3.1 and with tumor initiation, is frequently observed in prostate cancer (PCa). More significantly, loss of this region is associated with aggressiveness and poor prognosis of PCa, thereby emphasizing a key role of this region in advanced prostate cancer. In a paradigm shifting hypothesis, we proposed that this frequently deleted locus is associated with a cluster of miRNA genes - miR-3622a/b and miR-383- that are lost in PCa and play an important mechanistic role in PCa progression and metastasis by regulating Epithelial-mesenchymal-transition (EMT) and stemness. Extending our hypothesis, in this study we evaluated the role of miR-4287, a miRNA gene located within this region in PCa. We profiled the expression of miR-4287 in laser capture microdissected (LCM) PCa tissues and matched adjacent normal regions by real time PCR. miR-4287 expression was down regulated in ~79% of tissue samples. High miR-4287 expression was observed in 20% of cases. Analyses of miR-4287 expression in prostate cell lines showed that its expression is specifically attenuated in PCa cell lines compared to normal or immortalized prostate epithelial cells. Further, we evaluated the functional role of miR-4287 in prostate cancer by overexpressing miR-4287 precursor in PCa cell lines PC3 and LNCaP. miR-4287 overexpression in PCa cell lines led to decreased cellular viabilities as compared to control cells. Moreover, PCa cell lines overexpressing miR-4287 showed an increase in apoptosis and G0/G1 arrest. Further, we found that miR-4287 inhibits epithelial to mesenchymal transition (EMT) in PCa as its overexpression in PCa cell lines led to increased E-cadherin and decreased vimentin expression concomitant with morphological changes consistent with mesenchymal to epithelial transition (MET). We identified SRC, SFPR4 and CD44 as potential miR-4287 targets. Taken together, our data suggests that miR-4287 plays a significant role as tumor suppressor in PCa pathogenesis. Citation Format: Divya Bhagirath, Thao Yang, Laura Tabatabai, Shahana Majid, Soichiro Yamamura, Rajvir Dahiya, Yuichiro Tanaka, Sharanjot Saini. Role of novel microRNA 4287 at a frequently deleted chromosome 8p region in prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3565.