Inhibition of autophagy and tumor growth in colon cancer by miR-502

Oncogene. 2013 Mar 21;32(12):1570-9. doi: 10.1038/onc.2012.167. Epub 2012 May 14.

Abstract

Autophagy is a catabolic process that allows cellular macromolecules to be broken down and recycled as metabolic precursors. The influence of non-coding microRNAs in autophagy has not been explored in colon cancer. In this study, we discover a novel mechanism of autophagy regulated by hsa-miR-502-5p (miR-502) by suppression of Rab1B, a critical mediator of autophagy. A number of other miR-502 suppressed mRNA targets (for example, dihydroorotate dehydrogenase) are also identified by microarray analysis. Ectopic expression of miR-502 inhibited autophagy, colon cancer cell growth and cell-cycle progression of colon cancer cells in vitro. miR-502 also inhibited in-vivo colon cancer growth in a mouse tumor xenografts model. In addition, the expression of miR-502 was regulated by p53 via a negative feedback regulatory mechanism. The expression of miR-502 was downregulated in colon cancer patient specimens compared with the paired normal control samples. These results suggest that miR-502 may function as a potential tumor suppressor and therefore be a novel candidate for developing miR-502-based therapeutic strategies.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autophagy / physiology*
  • Cell Line, Tumor
  • Cell Proliferation
  • Colonic Neoplasms / pathology*
  • Colonic Neoplasms / prevention & control
  • Cyclin-Dependent Kinase Inhibitor p21 / physiology
  • Dihydroorotate Dehydrogenase
  • Humans
  • MicroRNAs / physiology*
  • Oxidoreductases Acting on CH-CH Group Donors / genetics
  • Tumor Suppressor Protein p53 / physiology
  • rab1 GTP-Binding Proteins / genetics

Substances

  • CDKN1A protein, human
  • Cyclin-Dependent Kinase Inhibitor p21
  • Dihydroorotate Dehydrogenase
  • MIRN502 microRNA, human
  • MicroRNAs
  • Tumor Suppressor Protein p53
  • Oxidoreductases Acting on CH-CH Group Donors
  • Rab1B protein, human
  • rab1 GTP-Binding Proteins