MiR-15a and MiR-16 Control Bmi-1 Expression in Ovarian Cancer

• Published in: Cancer research (Chicago, Ill.) Vol. 69; no. 23; pp. 9090 - 9095
• Main Authors: BHATTACHARYA, Resham, NICOLOSO, Milena, ARVIZO, Rochelle, ENFENG WANG, CORTEZ, Angelica, ROSSI, Simona, CALIN, George A, MUKHERJEE, Priyabrata
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01.12.2009
• Subjects: 3' Untranslated Regions; Antineoplastic agents; Biological and medical sciences; Cell Growth Processes - genetics; Cell Line, Tumor; Female; Female genital diseases; Gene Expression Regulation, Neoplastic; Gynecology. Andrology. Obstetrics; Humans; Medical sciences; MicroRNAs - genetics; Nuclear Proteins - biosynthesis; Nuclear Proteins - genetics; Ovarian Neoplasms - genetics; Ovarian Neoplasms - metabolism; Ovarian Neoplasms - pathology; Pharmacology. Drug treatments; Polycomb Repressive Complex 1; Proto-Oncogene Proteins - biosynthesis; Proto-Oncogene Proteins - genetics; Repressor Proteins - biosynthesis; Repressor Proteins - genetics; Transfection; Tumors; RNA interference; Ovary cancer; Micro RNA; Malignant tumor; Gene expression; Female genital diseases; Ovarian diseases; Gene silencing; Control; BMI1 gene; C-Onc gene; Protooncogene; Cancer
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/0008-5472.can-09-2552

Oncogenic activation of Bmi-1 is found in a wide variety of epithelial malignancies including ovarian cancer, yet a specific mechanism for overexpression of Bmi-1 has not been determined. Thus, realizing the immense pathologic significance of Bmi-1 in cancer, we wanted to investigate if microRNA (miRNA) aberrations played a role in the regulation of Bmi-1 in ovarian cancer. In this report, we identify two miRNAs, miR-15a and miR-16, that are underexpressed in ovarian cell lines and in primary ovarian tissues. We show that these miRNAs directly target the Bmi-1 3' untranslated region and significantly correlate with Bmi-1 protein levels in ovarian cancer patients and cell lines. Furthermore, Bmi-1 protein levels are downregulated in response to miR-15a or miR-16 expression and lead to significant reduction in ovarian cancer cell proliferation and clonal growth. These findings suggest the development of therapeutic strategies by restoring miR-15a and miR-16 expression in ovarian cancer and in other cancers that involve upregulation of Bmi-1.