Coordinate suppression of ERBB2 and ERBB3 by enforced expression of micro-RNA miR-125a or miR-125b.

摘要: Deregulation of micro-RNAs (miRNAs) is emerging as a major aspect cancer etiology because their capacity to direct the translation and stability targeted transcripts can dramatically influence cellular physiology. To explore potential exogenously applied miRNAs suppress oncogenic proteins, ERBB oncogene family was chosen with bioinformatics search identifying targeting seed sequences for miR-125a miR-125b within 3′-untranslated regions both ERBB2 ERBB3. Using human breast cell line SKBR3 model ERBB3 dependence, infection these cells retroviral constructs expressing either or resulted in suppression at transcript protein level. Luciferase containing 3′ demonstrated ∼35% less activity miR-125a- miR-125b-expressing relative controls. Additionally, phosphorylation ERK1/2 AKT suppressed overexpressing miR-125b. Consistent signaling, miR-125a-or miR-125b-overexpressing were impaired anchorage-dependent growth exhibited reduced migration invasion capacities. Parallel studies performed on MCF10A that overexpression produced only marginal influences non-transformed mammary epithelial cells. These results illustrate feasibility using therapeutic strategy expression function.