title: RNF216 contributes to proliferation and migration of colorectal cancer via suppressing BECN1-dependent autophagy.
abstract: Originally identified as an E3 ligase regulating toll-like receptor (TLR) signaling, ring finger protein 216 (RNF216) also plays an essential role in autophagy, which is fundamental to cellular homeostasis. Autophagy dysfunction leads to an array of pathological events, including tumor formation. In this study, we found that RNF216 was upregulated in human colorectal cancer (CRC) tissues and cell lines, and was associated with progression of CRC. RNF216 promoted CRC cell proliferation and migration in vitro and in vivo, largely by enhancing proteasomal degradation of BECN1, a key autophagy regulator and tumor suppressor. RNF216 restricted CRC cell autophagy through BECN1 inhibition under nutritional starvation conditions. RNF216 knockdown increased the autophagy, limiting CRC cell proliferation and migration. Moreover, BECN1 knockdown or autophagy inhibition restored proliferation and migration of RNF216-knockdown CRC cells. Collectively, our results suggested that RNF216 promoted CRC cell proliferation and migration by negatively regulating BECN1-dependent autophagy. This makes RNF216 as a potential biomarker and novel therapeutic target for inhibiting CRC development and progression.
authors.affiliation: Shanghai Institute of Immunology, Institutes of Medical Sciences, Shanghai Jiao Tong University School of Medicine (SJTUSM) and Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences & SJTUSM, Shanghai, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.affiliation: Shanghai Institute of Immunology, Institutes of Medical Sciences, Shanghai Jiao Tong University School of Medicine (SJTUSM) and Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences & SJTUSM, Shanghai, China.
authors.forename: Yanan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Shanghai Institute of Immunology, Institutes of Medical Sciences, Shanghai Jiao Tong University School of Medicine (SJTUSM) and Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences & SJTUSM, Shanghai, China.
authors.forename: Liu
authors.initials: L
authors.lastname: Qian
authors.affiliation: Shanghai Institute of Immunology, Institutes of Medical Sciences, Shanghai Jiao Tong University School of Medicine (SJTUSM) and Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences & SJTUSM, Shanghai, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China.
authors.forename: Hailiang
authors.initials: H
authors.lastname: Gu
authors.affiliation: Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China.
authors.forename: Xiaoqiang
authors.initials: X
authors.lastname: Dong
authors.affiliation: Shanghai Institute of Immunology, Institutes of Medical Sciences, Shanghai Jiao Tong University School of Medicine (SJTUSM) and Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences & SJTUSM, Shanghai, China.
authors.forename: Shiqian
authors.initials: S
authors.lastname: Huang
authors.affiliation: Shanghai Institute of Immunology, Institutes of Medical Sciences, Shanghai Jiao Tong University School of Medicine (SJTUSM) and Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences & SJTUSM, Shanghai, China.
authors.forename: Min
authors.initials: M
authors.lastname: Jin
authors.affiliation: Shanghai Institute of Immunology, Institutes of Medical Sciences, Shanghai Jiao Tong University School of Medicine (SJTUSM) and Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences & SJTUSM, Shanghai, China.
authors.forename: Hailiang
authors.initials: H
authors.lastname: Ge
authors.affiliation: Shanghai Institute of Immunology, Institutes of Medical Sciences, Shanghai Jiao Tong University School of Medicine (SJTUSM) and Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences & SJTUSM, Shanghai, China.
authors.forename: Congfeng
authors.initials: C
authors.lastname: Xu
authors.affiliation: Shanghai Institute of Immunology, Institutes of Medical Sciences, Shanghai Jiao Tong University School of Medicine (SJTUSM) and Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences & SJTUSM, Shanghai, China.
authors.forename: Yanyun
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001343:Autophagy / Q000235:genetics*; D000071186:Beclin-1 / Q000235:genetics / Q000502:physiology*; D014408:Biomarkers, Tumor / Q000235:genetics; D018938:Caco-2 Cells; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics*; D049109:Cell Proliferation / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor / Q000502:physiology; D019073:HT29 Cells; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000502:physiology*
chemical_list: C491997:BECN1 protein, human; D000071186:Beclin-1; D014408:Biomarkers, Tumor; C458527:RNF216 protein, human; D044767:Ubiquitin-Protein Ligases
keywords: BECN1; RNF216; autophagy; colorectal cancer