MiR-15a and MiR-16 control Bmi-1 expression in ovarian cancer

Resham Bhattacharya, Milena Nicoloso, Rochelle Arvizo, Enfeng Wang, Angelica Cortez, Simona Rossi, George A. Calin, Priyabrata Mukherjee

Research output: Contribution to journalArticlepeer-review

205 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)9090-9095
Number of pages6
JournalCancer research
Volume69
Issue number23
DOIs
StatePublished - Dec 1 2009

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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