Distinct microRNA Expression Profiles in Prostate Cancer Stem/Progenitor Cells and Tumor-Suppressive Functions of let-7

• Published in: Cancer research (Chicago, Ill.) Vol. 72; no. 13; pp. 3393 - 3404
• Main Authors: CAN LIU, KELNAR, Kevin, VLASSOV, Alexander V, BROWN, David, JUNCHEN WANG, TANG, Dean G
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01.07.2012
• Subjects: Antineoplastic agents; Biological and medical sciences; Gene Expression Profiling; Gynecology. Andrology. Obstetrics; Humans; Male; Male genital diseases; Medical sciences; MicroRNAs - genetics; MicroRNAs - physiology; Neoplastic Stem Cells - pathology; Nephrology. Urinary tract diseases; Pharmacology. Drug treatments; Prostatic Neoplasms - genetics; Prostatic Neoplasms - pathology; Tumors; Tumors of the urinary system; Urinary tract. Prostate gland; Urinary system disease; RNA interference; Prostate disease; Stem cell; Micro RNA; Malignant tumor; Gene expression; Profile; Gene silencing; Male genital diseases; Prostate cancer; Tumor cell; Cancer; Progenitor cell
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/0008-5472.can-11-3864

MiRNAs regulate cancer cells, but their potential effects on cancer stem/progenitor cells are still being explored. In this study, we used quantitative real-time-PCR to define miRNA expression patterns in various stem/progenitor cell populations in prostate cancer, including CD44+, CD133+, integrin α2β1+, and side population cells. We identified distinct and common patterns in these different tumorigenic cell subsets. Multiple tumor-suppressive miRNAs were downregulated coordinately in several prostate cancer stem/progenitor cell populations, namely, miR-34a, let-7b, miR-106a, and miR-141, whereas miR-301 and miR-452 were commonly overexpressed. The let-7 overexpression inhibited prostate cancer cell proliferation and clonal expansion in vitro and tumor regeneration in vivo. In addition, let-7 and miR-34a exerted differential inhibitory effects in prostate cancer cells, with miR-34a inducing G1 phase cell-cycle arrest accompanied by cell senescence and let-7 inducing G2-M phase cell-cycle arrest without senescence. Taken together, our findings define distinct miRNA expression patterns that coordinately regulate the tumorigenicity of prostate cancer cells.