MiRNA-708 control of CD44+ prostate cancer-initiating cells

Sharanjot Saini, Shahana Majid, Varahram Shahryari, Sumit Arora, Soichiro Yamamura, Inik Chang, Mohd Saif Zaman, Guoren Deng, Yuichiro Tanaka, Rajvir Dahiya

Research output: Contribution to journalArticle

86 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)3618-3630
Number of pages13
JournalCancer Research
Volume72
Issue number14
DOIs
StatePublished - Jul 15 2012
Externally publishedYes

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Saini, S., Majid, S., Shahryari, V., Arora, S., Yamamura, S., Chang, I., Zaman, M. S., Deng, G., Tanaka, Y., & Dahiya, R. (2012). MiRNA-708 control of CD44+ prostate cancer-initiating cells. Cancer Research, 72(14), 3618-3630. https://doi.org/10.1158/0008-5472.CAN-12-0540