Data from miRNA-708 Control of CD44<sup>+</sup> Prostate Cancer–Initiating Cells

Abstract

<div>Abstract<p>Tumor recurrence in prostate cancer has been attributed to the presence of CD44-expressing tumor-initiating cells. In this study, we report that miR-708 is a key negative regulator of this CD44<sup>+</sup> subpopulation of prostate cancer cells, with important implications for diagnosis and prognosis of this disease. miR-708 was underexpressed in CD44<sup>+</sup> cells from prostate cancer xenografts. Reconstitution of miR-708 in prostate cancer cell lines or CD44<sup>+</sup> prostate cancer cells led to decreased tumorigenicity <i>in vitro</i>. Intratumoral delivery of synthetic miR-708 oligonucleotides triggered regression of established tumors in a murine xenograft model of human prostate cancer. Conversely, miR-708 silencing in a purified CD44<sup>−</sup> population of prostate cancer cells promoted tumor growth. Functional studies validated CD44 to be a direct target of miR-708 and also identified the serine/threonine kinase AKT2 as an additional target. Clinically, low miR-708 expression was associated significantly with poor survival outcome, tumor progression, and recurrence in patients with prostate cancer. Together, our findings suggest that reduced miR-708 expression leads to prostate cancer initiation, progression, and development by regulating the expression of CD44 as well as AKT2. miR-708 therefore may represent a novel therapeutic target or diagnostic and prognostic biomarker in prostate cancer. <i>Cancer Res; 72(14); 3618–30. ©2012 AACR</i>.</p></div>