Preferential Star Strand Biogenesis of Pre-miR-24-2 Targets PKC-alpha and Suppresses Cell Survival in MCF-7 Breast Cancer Cells
| Autor: | Martin, Elizabeth C., Elliott, Steven, Rhodes, Lyndsay V., Antoon, James W., Fewell, Claire, Zhu, Yun, Driver, Jennifer L., Jodari-Karimi, Mona, Taylor, Christopher W., Flemington, Erik K., Beckman, Barbara S., Collins-Burow, Bridgette M., Burow, Matthew E. |
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| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Binding Sites
Protein Kinase C-alpha Base Sequence Cell Survival Breast Neoplasms Article Gene Expression Regulation Neoplastic Isoenzymes Mice MicroRNAs Cell Transformation Neoplastic Cell Line Tumor MCF-7 Cells Animals Humans Female RNA Interference skin and connective tissue diseases Base Pairing |
| Popis: | 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 PKCα. 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 PKCα-mediated cellular survival. |
| Databáze: | OpenAIRE |
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