title: 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.affiliation: Laboratory of Cancer Biology; Sir Runrun Shaw Hospital; School of Medicine; Zhejiang University; Hangzhou, Zhejiang China.
authors.forename: Lifeng
authors.initials: L
authors.lastname: Feng
authors.affiliation: Laboratory of Cancer Biology; Sir Runrun Shaw Hospital; School of Medicine; Zhejiang University; Hangzhou, Zhejiang China.
authors.forename: Yanning
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Laboratory of Cancer Biology; Sir Runrun Shaw Hospital; School of Medicine; Zhejiang University; Hangzhou, Zhejiang China.
authors.forename: Jie
authors.initials: J
authors.lastname: Sun
authors.affiliation: Department of Medical Oncology; Institute of Clinical Science; Sir Runrun Shaw Hospital; School of Medicine; Zhejiang University; Hangzhou, Zhejiang Province China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Shen
authors.affiliation: Laboratory of Cancer Biology; Sir Runrun Shaw Hospital; School of Medicine; Zhejiang University; Hangzhou, Zhejiang China.
authors.forename: Leiming
authors.initials: L
authors.lastname: Liu
authors.affiliation: Laboratory of Cancer Biology; Sir Runrun Shaw Hospital; School of Medicine; Zhejiang University; Hangzhou, Zhejiang China.
authors.forename: Haiqi
authors.initials: H
authors.lastname: Lu
authors.affiliation: Laboratory of Cancer Biology; Sir Runrun Shaw Hospital; School of Medicine; Zhejiang University; Hangzhou, Zhejiang China.
authors.forename: Faliang
authors.initials: F
authors.lastname: Wang
authors.affiliation: Laboratory of Cancer Biology; Sir Runrun Shaw Hospital; School of Medicine; Zhejiang University; Hangzhou, Zhejiang China.
authors.forename: Yongfang
authors.initials: Y
authors.lastname: Yue
authors.affiliation: Department of Medical Oncology; Institute of Clinical Science; Sir Runrun Shaw Hospital; School of Medicine; Zhejiang University; Hangzhou, Zhejiang Province China.
authors.forename: Jiaqiu
authors.initials: J
authors.lastname: Li
authors.affiliation: Laboratory of Cancer Biology; Sir Runrun Shaw Hospital; School of Medicine; Zhejiang University; Hangzhou, Zhejiang China.
authors.forename: Shenjie
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Laboratory of Cancer Biology; Sir Runrun Shaw Hospital; School of Medicine; Zhejiang University; Hangzhou, Zhejiang China.
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Lin
authors.affiliation: Laboratory of Cancer Biology; Sir Runrun Shaw Hospital; School of Medicine; Zhejiang University; Hangzhou, Zhejiang China.
authors.forename: Jue
authors.initials: J
authors.lastname: Chu
authors.affiliation: Department of Medical Oncology; Institute of Clinical Science; Sir Runrun Shaw Hospital; School of Medicine; Zhejiang University; Hangzhou, Zhejiang Province China.
authors.forename: Weidong
authors.initials: W
authors.lastname: Han
authors.affiliation: Department of Medical Oncology; Institute of Clinical Science; Sir Runrun Shaw Hospital; School of Medicine; Zhejiang University; Hangzhou, Zhejiang Province China.
authors.forename: Xian
authors.initials: X
authors.lastname: Wang
authors.affiliation: Laboratory of Cancer Biology; Sir Runrun Shaw Hospital; School of Medicine; Zhejiang University; Hangzhou, Zhejiang China.
authors.forename: Hongchuan
authors.initials: H
authors.lastname: Jin
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001343:Autophagy; D001483:Base Sequence; D045744:Cell Line, Tumor; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008954:Models, Biological; D008969:Molecular Sequence Data; D055550:Protein Stability; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D000071456:Sequestosome-1 Protein; D015398:Signal Transduction; D050986:YY1 Transcription Factor / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C561021:MIRN372 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; C099718:SQSTM1 protein, human; D000071456:Sequestosome-1 Protein; D050986:YY1 Transcription Factor; C494698:YY1 protein, human
keywords: MIR372; SQSTM1; YY1; autophagy; epigenetics