title: Brg-1 targeting of novel miR550a-5p/RNF43/Wnt signaling axis regulates colorectal cancer metastasis.
abstract: Metastasis is one of the main causes of death in patients with colorectal cancer (CRC). Brg-1 is a central component of the SWItch/Sucrose NonFermentable chromatin-remodeling complex, which features a bromodomain and helicase/ATPase activity. The gene encoding Brg-1 is frequently mutated or silenced in human cancers. Several reports have proposed Brg-1 as a tumor suppressor; however, little is known about its role in oncogenesis and metastasis. Here we demonstrated that decreased Brg-1 regulates a novel miR-550a-5p/RNF43/Wnt/β-catenin signaling pathway, to promote CRC metastasis in vitro and in vivo. In particular, we used high-throughput RNA-sequencing analysis to show that Brg-1 negatively regulates miR-550a-5p in CRC cells. We further found that Brg-1 inhibits the transcriptional activity of miR-550a-5p promoter, and that decreased Brg-1 expression increased miR-550a-5p expression. We also identified ring finger 43 (RNF43), an inhibitor of Wnt/β-catenin signaling, as a target of miR-550a-5p. Knockdown of Brg-1 by small interfering RNA led to decreased RNF43 expression, increased Wnt signaling and increased CRC cell migration and invasion. This novel pathway defines a new function for Brg-1 and provides potential targets for the treatment of Brg-1 mutant and loss-of-function tumors.
authors.affiliation: Cancer Research Institute, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: G
authors.initials: G
authors.lastname: Wang
authors.affiliation: Cancer Research Institute, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Fu
authors.affiliation: Cancer Research Institute, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: X
authors.initials: X
authors.lastname: Yang
authors.affiliation: Cancer Research Institute, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: X
authors.initials: X
authors.lastname: Luo
authors.affiliation: Department of Immunology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: J
authors.initials: J
authors.lastname: Wang
authors.affiliation: Molecular Medical Center, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: J
authors.initials: J
authors.lastname: Gong
authors.affiliation: Cancer Research Institute, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: J
authors.initials: J
authors.lastname: Hu
mesh_terms: D000818:Animals; D018938:Caco-2 Cells; D002465:Cell Movement / Q000502:physiology; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D005260:Female; D055785:Gene Knockdown Techniques; D045325:HCT116 Cells; D019073:HT29 Cells; D064593:Heterografts; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016688:Mice, Inbred NOD; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D015513:Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D044767:Ubiquitin-Protein Ligases; D060449:Wnt Signaling Pathway
chemical_list: D004268:DNA-Binding Proteins; D035683:MicroRNAs; D009687:Nuclear Proteins; D015513:Oncogene Proteins; D014157:Transcription Factors; C496945:RNF43 protein, human; D044767:Ubiquitin-Protein Ligases; C084108:SMARCA4 protein, human; D004265:DNA Helicases