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miRNA-708 Control of CD44+ Prostate Cancer--Initiating Cells.
- Source :
-
Cancer Research . Jul2012, Vol. 72 Issue 14, p3618-3630. 13p. - Publication Year :
- 2012
-
Abstract
- 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+ subpopulation of prostate cancer cells, with important implications for diagnosis and prognosis of this disease. miR-708 was underexpressed in CD44+ cells from prostate cancer xenografts. Reconstitution of miR-708 in prostate cancer cell lines or CD44+ prostate cancer cells led to decreased tumorigenicity in vitro. 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- 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. [ABSTRACT FROM AUTHOR]
- Subjects :
- *CD44 antigen
*PROSTATE cancer
*TUMORS
*XENOGRAFTS
*CANCER cells
Subjects
Details
- Language :
- English
- ISSN :
- 00085472
- Volume :
- 72
- Issue :
- 14
- Database :
- Academic Search Index
- Journal :
- Cancer Research
- Publication Type :
- Academic Journal
- Accession number :
- 85969010
- Full Text :
- https://doi.org/10.1158/0008-5472.CAN-12-0540