Regulation of autophagy by a beclin 1-targeted microRNA, miR-30a, in cancer cells

Hua Zhu, Hao Wu, Xiuping Liu, Biao Li, Yun Chen, Xingcong Ren, Chang Gong Liu, Jin Ming Yang

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323 Scopus citations

Abstract

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 1 is altered in certain diseases including cancers. The causes underlying the aberrant expression of beclin 1 remain 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 1 expression and autophagy. We demonstrated that beclin 1 is a potential target for miRNA miR-30a, and this miRNA could negatively regulate beclin 1 expression resulting in decreased autophagic activity. Treatment of tumor cells with the miR-30a mimic decreased, and with the antagomir increased, the expression of beclin 1 mRNA and protein. Dual luciferase reporter assay confirmed that the miR-30a binding sequences in the 3′-UTR of beclin 1 contribute to the modulation of beclin 1 expression by miR-30a. Furthermore, inhibition of beclin 1 expression by the miR-30a mimic blunted activation of autophagy induced by rapamycin. Our study of the role of miR-30a in regulating beclin 1 expression 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.

Original languageEnglish (US)
Pages (from-to)816-823
Number of pages8
JournalAutophagy
Volume5
Issue number6
DOIs
StatePublished - Aug 16 2009

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

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    Zhu, H., Wu, H., Liu, X., Li, B., Chen, Y., Ren, X., Liu, C. G., & Yang, J. M. (2009). Regulation of autophagy by a beclin 1-targeted microRNA, miR-30a, in cancer cells. Autophagy, 5(6), 816-823. https://doi.org/10.4161/auto.9064