Title: VHL-regulated MiR-204 suppresses tumor growth through inhibition of LC3B-mediated autophagy in renal clear cell carcinoma.
Authors: Mikhaylova, Olga; Stratton, Yiwen; Hall, Daniel; Kellner, Emily; Ehmer, Birgit; Drew, Angela F; Gallo, Catherine A; Plas, David R; Biesiada, Jacek; Meller, Jarek; Czyzyk-Krzeska, Maria F
Published In Cancer Cell, (2012 Apr 17)
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.
PubMed ID: 22516261
MeSH Terms: Animals; Autophagy/genetics*; Carcinoma, Renal Cell/genetics*; Carcinoma, Renal Cell/pathology; Humans; Kidney Neoplasms/genetics*; Kidney Neoplasms/pathology; Mice; MicroRNAs/genetics; MicroRNAs/physiology*; Microtubule-Associated Proteins/physiology*; Transplantation, Heterologous/pathology; Tumor Cells, Cultured; Von Hippel-Lindau Tumor Suppressor Protein/genetics*