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Cancer Cell. 2012 Apr 17;21(4):532-46. doi: 10.1016/j.ccr.2012.02.019.

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

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  • 1Department of Cancer and Cell Biology, University of Cincinnati College of Medicine, Cincinnati, OH 45267-0056, USA.

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.

Copyright © 2012 Elsevier Inc. All rights reserved.

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PMID:
22516261
[PubMed - indexed for MEDLINE]
PMCID:
PMC3331999
Free PMC Article

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