4.6 Article

Preferential Star Strand Biogenesis of Pre-miR-24-2 Targets PKC-Alpha and Suppresses Cell Survival in MCF-7 Breast Cancer Cells

Journal

MOLECULAR CARCINOGENESIS
Volume 53, Issue 1, Pages 38-+

Publisher

WILEY
DOI: 10.1002/mc.21946

Keywords

miRNA maturation; PKC cellular survival; breast cancer; strand preference; miR-24-2*

Funding

  1. National Institutes of Health, National Cancer Institute [R01CA 125806-01A2]
  2. Office of Naval Research [N00014-16-1-1136]
  3. National Center for Research Resources [P20RR020152]

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microRNAs (miRNA) are regulators of cellular pathways and alterations of normal miRNA expression levels have been shown to increase tumorigenesis. miR-24 has been demonstrated as having both tumor suppressive and oncogenic properties depending on cell context. Here, we demonstrate a possible role for pre-miR-24-2 as a tumor suppressor in the MCF-7 breast cancer cell line through the preferential processing of mature miR-24-2* over miR-24. Specifically, we show that the ectopic expression of miR-24-2* in MCF-7 breast cancer cells results in a suppression of cellular survival both in vivo and in vitro. Notably, the overexpression of miR-24-2* results in a dampening of cell survival through the targeted suppression of PKC. In addition, a similar biological change is observed in vivo where MCF-7 cells overexpressing pre-miR-24-2 have decreased tumorigenicity and tumor incidence. Taken together our data demonstrate that when overexpressed biogenesis of the pre-miR-24-2 favors miR-24-2* in the MCF-7 breast cancer cell line and suggests a tumor suppressive role for miR-24-2* observed through the inhibition of PKC-mediated cellular survival. (c) 2013 Wiley Periodicals, Inc.

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