VHL-regulated MiR-204 suppresses tumor growth through inhibition of LC3B-mediated autophagy in renal clear cell carcinoma.

作者: Olga Mikhaylova , Yiwen Stratton , Daniel Hall , Emily Kellner , Birgit Ehmer

DOI: 10.1016/J.CCR.2012.02.019

关键词: Clear cellCell biologyMAP1LC3BCellBiologyTransplantationmicroRNASuppressorAutophagyRegulator

摘要: The von Hippel-Lindau tumor-suppressor gene (VHL) is lost in most clear cell renal carcinomas (ccRCC). Here, using human ccRCC specimens, VHL-deficient cells, and xenograft models, we show that miR-204 a VHL-regulated tumor suppressor acting by inhibiting macroautophagy, with MAP1LC3B (LC3B) as direct functional target. Of note, higher grade of was correlated concomitant decrease increase LC3B levels, indicating LC3B-mediated macroautophagy necessary for RCC progression. VHL, addition to inducing endogenous miR-204, triggered the expression LC3C, an HIF-regulated paralog, suppressed growth. These data reveal function VHL tumor-suppressing regulator autophagic programs.

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