Molecular Carcinogenesis · 2012 · 51 citations · 42 references
Life SciencesMolecular BiologyOncologyCarcinogenesisGene ExpressionMolecular OncologyCancer ProgressionMicrorna BiogenesisMicrorna BiologyMicrorna-mediated RegulationNoncoding Rna In CancerTumor Suppressor GenesCancer Cell Line ModelsMicrorna Function In CancerMicrorna In CancerMicrorna MaturationMicrorna Regulation In CancerOncogenic TransformationSuppressionTumor Suppressor Pathways
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.
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