부산대학교 도서관

beclin 1, the mammalian homologue of the yeast Atg6, is a key autophagy-promoting gene that plays a critical role in the regulation of cell death and survival of various types of cells. However, recent studies have observed that the expression of beclin 1is altered in certain diseases including cancers. The causes underlying the aberrant expression of beclin 1remain largely unknown. We report here that microRNAs (miRNAs), a class of endogenous, 22–24 nucleotide noncoding RNA molecules able to affect stability and translation of mRNA, may represent a previously unrecognized mechanism for regulating beclin 1expression and autophagy. We demonstrated that beclin 1is a potential target for miRNA miR-30a, and this miRNA could negatively regulate beclin 1expression resulting in decreased autophagic activity. Treatment of tumor cells with the miR-30a mimic decreased, and with the antagomir increased, the expression of beclin 1mRNA and protein. Dual luciferase reporter assay confirmed that the miR-30a binding sequences in the 3′-UTR of beclin 1contribute to the modulation of beclin 1expression by miR-30a. Furthermore, inhibition of beclin 1expression by the miR-30a mimic blunted activation of autophagy induced by rapamycin. Our study of the role of miR-30a in regulating beclin 1expression and autophagy reveals a novel function for miRNA in a critical cellular event with significant impacts in cancer development, progression and treatment, and in other diseases.