Author/Authors :
Mikhaylova، نويسنده , , Olga and Stratton، نويسنده , , Yiwen and Hall، نويسنده , , Daniel and Kellner، نويسنده , , Emily and Ehmer، نويسنده , , Birgit and Drew، نويسنده , , Angela F. and Gallo، نويسنده , , Catherine A. and Plas، نويسنده , , David R. and Biesiada، نويسنده , , Jacek and Meller، نويسنده , , Jarek and Czyzyk-Krzeska، نويسنده , , Maria F.، نويسنده ,
Abstract :
Summary
n 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.
