Negative regulation of CDC42 expression and cell cycle progression by miR-29a in breast cancer.

Abstract

ObjectiveThe inhibitory role of microRNA-29a (miR-29a) has been assessed in breast cancer cells. Herein, we analyze the underlying mechanisms of its role in cell cycle progression in breast cancer cells.MethodsWe applied real-time polymerase chain reaction (PCR) to detect the expression of miR-29 in breast cancer cell lines. Then one of the cell lines, MDA-MB-453, was transfected with mimics of miR-29a. The cell cycle was analyzed by fluorescence-activated cell sorting after staining the cells with propidium iodide. Real-time PCR, luciferase assay and western blot were used together to verify the regulation of the predicted target, cell division cycle 42 (CDC42) by miR-29a.ResultsMiR-29s were decreased in our selected mammary cell lines, among which miR-29a was the dominant isoform. Overexpression of miR-29a caused cell cycle arrest at the G0/G1 phase. We further found that miR-29a could target the expression of CDC42, which is a small GTPase associated with cell cycle progression.ConclusionWe suggest that miR-29a exerts its tumor suppressor role in breast cancer cells partially by arresting the cell cycle through negative regulation of CDC42.