Upregulation of miR-96 Enhances Cellular Proliferation of Prostate Cancer Cells through FOXO1.

Summary, in English

Aberrant expression of miR-96 in prostate cancer has previously been reported. However, the role and mechanism of action of miR-96 in prostate cancer has not been determined. In this study, the diagnostic and prognostic properties of miR-96 expression levels were investigated by qRT-PCR in two well documented prostate cancer cohorts. The miR-96 expression was found to be significantly higher in prostate cancer patients and correlate with WHO grade, and decreased overall survival time; patients with low levels of miR-96 lived 1.5 years longer than patients with high miR-96 levels. The therapeutic potential was further investigated in vitro, showing that ectopic levels of miR-96 enhances growth and cellular proliferation in prostate cancer cells, implying that miR-96 has oncogenic properties in this setting. We demonstrate that miR-96 expression decreases the transcript and protein levels of FOXO1 by binding to one of two predicted binding sites in the FOXO1 3'UTR sequence. Blocking this binding site completely inhibited the growth enhancement conveyed by miR-96. This finding was corroborated in a large external prostate cancer patient cohort where miR-96 expression inversely correlated to FOXO1 expression. Taken together these findings indicate that miR-96 plays a key role in prostate cancer cellular proliferation and can enhance prostate cancer progression. This knowledge might be utilized for the development of novel therapeutic tools for prostate cancer.

• Författare: Benedikta Haflidadottir; Olivia Larne; Myriam Martin; Margareta Persson; Anders Edsjö; Anders Bjartell; Yvonne Ceder
• Avdelning/ar: Klinisk kemi, Malmö; Proteinkemi, Malmö; Institutionen för translationell medicin; Medicinsk molekylärbiologi; EpiHealth: Epidemiology for Health; BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation
• Publiceringsår: 2013
• Språk: Engelska
• Publikation/Tidskrift/Serie: PLoS ONE
• Volym: 8
• Issue: 8
• Fulltext: - 702 kB; Download statistics
• Länkar: http://www.ncbi.nlm.nih.gov/pubmed/23951320?dopt=Abstract; http://dx.doi.org/10.1371/journal.pone.0072400
• Dokumenttyp: Artikel i tidskrift
• Förlag: Public Library of Science (PLoS)
• Ämne: Cancer and Oncology; Urology and Nephrology; Medicinal Chemistry
• Status: Published
• Forskningsgrupp: Clinical Chemistry, Malmö; Protein Chemistry, Malmö; Medical Molecular Biology
• ISBN/ISSN/Övrigt: ISSN: 1932-6203