VHL-regulated MiR-204 Suppresses Tumor Growth Through Inhibition of LC3B-mediated Autophagy in Renal Clear Cell Carcinoma

Overview

Journal Cancer Cell

Publisher Cell Press

Specialty Oncology

Date 2012 Apr 21

PMID 22516261

Citations 167

Authors

Olga Mikhaylova

Yiwen Stratton

Daniel Hall

Emily Kellner

Birgit Ehmer

Angela F Drew

Catherine A Gallo

David R Plas

Jacek Biesiada

Jarek Meller

Maria F Czyzyk-Krzeska

Affiliations

Soon will be listed here.

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.

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