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miRNA-708 Control of CD44(+) Prostate Cancer-Initiating Cells

Authors
 Sharanjot Saini ; Shahana Majid ; Rajvir Dahiya ; Yuichiro Tanaka ; Guoren Deng ; Mohd Saif Zaman ; Inik Chang ; Soichiro Yamamura ; Sumit Arora ; Varahram Shahryari 
Citation
 Cancer Research, Vol.72(14) : 3618~3630, 2012 
Journal Title
 Cancer Research 
ISSN
 0008-5472 
Issue Date
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.
URI
http://ir.ymlib.yonsei.ac.kr/handle/22282913/89876
DOI
10.1158/0008-5472.CAN-12-0540
Appears in Collections:
1. 연구논문 > 2. College of Dentistry > Dept. of Oral Biology
Yonsei Authors
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