YY1-MIR372-SQSTM1 regulatory axis in autophagy.

Abstract	Autophagy is a self-proteolytic process that degrades intracellular material to enable cellular survival under unfavorable conditions. However, how autophagy is activated in human carcinogenesis remains largely unknown. Herein we report an epigenetic regulation of autophagy in human cancer cells. YY1 (YY1 transcription factor) is a well-known epigenetic regulator and is upregulated in many cancers. We found that YY1 knockdown inhibited cell viability and autophagy flux through downregulating SQSTM1 (sequestosome 1). YY1 regulated SQSTM1 expression through the epigenetic modulation of the transcription of MIR372 (microRNA 372) which was found to target SQSTM1 directly. During nutrient starvation, YY1 was stimulated to promote SQSTM1 expression and subsequent autophagy activation by suppressing MIR372 expression. Similar to YY1 depletion, MIR372 overexpression blocked autophagy activation and inhibited in vivo tumor growth. SQSTM1 upregulation and competent autophagy flux thus contributed to the oncogenic function of YY1. YY1-promoted SQSTM1 upregulation might be a useful histological marker for cancer detection and a potential target for drug development.
Authors	Lifeng Feng, Yanning Ma, Jie Sun, Qi Shen, Leiming Liu, Haiqi Lu, Faliang Wang, Yongfang Yue, Jiaqiu Li, Shenjie Zhang, Xiaoying Lin, Jue Chu, Weidong Han, Xian Wang, Hongchuan Jin
Journal	Autophagy (Autophagy) Vol. 10 Issue 8 Pg. 1442-53 (Aug 2014) ISSN: 1554-8635 [Electronic] United States
PMID	24991827 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Adaptor Proteins, Signal Transducing MIRN372 microRNA, human MicroRNAs RNA, Messenger SQSTM1 protein, human Sequestosome-1 Protein YY1 Transcription Factor YY1 protein, human
Topics	Adaptor Proteins, Signal Transducing (genetics, metabolism) Animals Autophagy Base Sequence Cell Line, Tumor Down-Regulation Gene Expression Regulation, Neoplastic Humans Mice, Nude MicroRNAs (genetics, metabolism) Models, Biological Molecular Sequence Data Protein Stability RNA, Messenger (genetics, metabolism) Sequestosome-1 Protein Signal Transduction YY1 Transcription Factor (metabolism)

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