title: VHL-regulated MiR-204 suppresses tumor growth through inhibition of LC3B-mediated autophagy in renal clear cell carcinoma.
abstract: The von Hippel-Lindau tumor-suppressor gene (VHL) is lost in most clear cell renal cell carcinomas (ccRCC). Here, using human ccRCC specimens, VHL-deficient cells, and xenograft models, we show that miR-204 is a VHL-regulated tumor suppressor acting by inhibiting macroautophagy, with MAP1LC3B (LC3B) as a direct and functional target. Of note, higher tumor grade of human ccRCC was correlated with a concomitant decrease in miR-204 and increase in LC3B levels, indicating that LC3B-mediated macroautophagy is necessary for RCC progression. VHL, in addition to inducing endogenous miR-204, triggered the expression of LC3C, an HIF-regulated LC3B paralog, that suppressed tumor growth. These data reveal a function of VHL as a tumor-suppressing regulator of autophagic programs.
authors.affiliation: Department of Cancer and Cell Biology, University of Cincinnati College of Medicine, Cincinnati, OH 45267-0056, USA.
authors.forename: Olga
authors.initials: O
authors.lastname: Mikhaylova
authors.forename: Yiwen
authors.initials: Y
authors.lastname: Stratton
authors.forename: Daniel
authors.initials: D
authors.lastname: Hall
authors.forename: Emily
authors.initials: E
authors.lastname: Kellner
authors.forename: Birgit
authors.initials: B
authors.lastname: Ehmer
authors.forename: Angela F
authors.initials: AF
authors.lastname: Drew
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Gallo
authors.forename: David R
authors.initials: DR
authors.lastname: Plas
authors.forename: Jacek
authors.initials: J
authors.lastname: Biesiada
authors.forename: Jarek
authors.initials: J
authors.lastname: Meller
authors.forename: Maria F
authors.initials: MF
authors.lastname: Czyzyk-Krzeska
mesh_terms: D000818:Animals; D001343:Autophagy / Q000235:genetics*; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000473:pathology; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics* / Q000473:pathology; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000502:physiology*; D008869:Microtubule-Associated Proteins / Q000502:physiology*; D014183:Transplantation, Heterologous / Q000473:pathology; D014407:Tumor Cells, Cultured; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000235:genetics*
chemical_list: C502070:MAP1LC3B protein, human; C549404:MIRN204 microRNA, human; D035683:MicroRNAs; D008869:Microtubule-Associated Proteins; D051794:Von Hippel-Lindau Tumor Suppressor Protein