MiR-34a suppresses mutagenesis by inducing apoptosis in human lymphoblastoid TK6 cells

Abstract

miR-34a, a tumor suppressor miRNA, has been identified as a direct transcriptional target of P53. miRNA precursors and inhibitors have been used to modulate the expression of their targeted mRNA and thereby study miRNA functions. We indicated in our previous work that X-ray induces miR-34a expression in a time and dose dependent manner. The objective of this study was to elucidate the role of miR-34a in X-ray-induced mutations in human lymphoblast TK6 cells. Neither over-expression of miR-34a by lipid transfection of miR-34a precursor nor down regulation of endogenous miR-34a by miR-34a inhibitor had any effect on X-ray-induced micronucleus frequency in TK6 cells. Over-expression of miR-34a in TK6 cells significantly reduced X-ray induced mutant frequency (MF) in the Thymidine Kinase (TK) locus while suppression of endogenous miR-34a can increase the background level MF in TK6 cells. Furthermore, over-expression of miR-34a promoted and down-regulation of miR-34a inhibited background and X-ray-induced apoptosis in TK6 cells. Our study suggests miR-34a is an important negative regulator of mutagenesis and the mechanism is possibly mediated through apoptosis.