title: Inhibition of autophagy and tumor growth in colon cancer by miR-502.
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.
authors.affiliation: Department of Pathology, Translational Research Laboratory, Stony Brook University, Stony Brook, NY 11794-8691, USA.
authors.forename: H
authors.initials: H
authors.lastname: Zhai
authors.forename: B
authors.initials: B
authors.lastname: Song
authors.forename: X
authors.initials: X
authors.lastname: Xu
authors.forename: W
authors.initials: W
authors.lastname: Zhu
authors.forename: J
authors.initials: J
authors.lastname: Ju
mesh_terms: D001343:Autophagy / Q000502:physiology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003110:Colonic Neoplasms / Q000473:pathology* / Q000517:prevention & control; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000502:physiology; D000090722:Dihydroorotate Dehydrogenase; D006801:Humans; D035683:MicroRNAs / Q000502:physiology*; D044925:Oxidoreductases Acting on CH-CH Group Donors / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000502:physiology; D020761:rab1 GTP-Binding Proteins / Q000235:genetics
chemical_list: C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D000090722:Dihydroorotate Dehydrogenase; C545730:MIRN502 microRNA, human; D035683:MicroRNAs; D016159:Tumor Suppressor Protein p53; D044925:Oxidoreductases Acting on CH-CH Group Donors; C529587:Rab1B protein, human; D020761:rab1 GTP-Binding Proteins