title: Downregulation of RBMS3 is associated with poor prognosis in esophageal squamous cell carcinoma.
abstract: Deletions on chromosome 3p occur often in many solid tumors, including esophageal squamous cell carcinoma (ESCC), suggesting the existence at this location of one or more tumor suppressor genes (TSG). In this study, we characterized RBMS3 gene encoding an RNA-binding protein as a candidate TSG located at 3p24. Downregulation of RBMS3 mRNA and protein levels was documented in approximately 50% of the primary ESCCs examined. Clinical association studies determined that RBMS3 downregulation was associated with poor clinical outcomes. RBMS3 expression effectively suppressed the tumorigenicity of ESCC cells in vitro and in vivo, including by inhibition of cell growth rate, foci formation, soft agar colony formation, and tumor formation in nude mice. Molecular analyses revealed that RBMS3 downregulated c-Myc and CDK4, leading to subsequent inhibition of Rb phosphorylation. Together, our findings suggest a tumor suppression function for the human RBMS3 gene in ESCC, acting through c-Myc downregulation, with genetic loss of this gene in ESCC contributing to poor outcomes in this deadly disease.
authors.affiliation: State Key Laboratory of Oncology in Southern China, Cancer Center, Sun Yat-sen University, Guangzhou, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Leilei
authors.initials: L
authors.lastname: Chen
authors.forename: Chang-jun
authors.initials: CJ
authors.lastname: Nie
authors.forename: Ting-ting
authors.initials: TT
authors.lastname: Zeng
authors.forename: Haibo
authors.initials: H
authors.lastname: Liu
authors.forename: Xueying
authors.initials: X
authors.lastname: Mao
authors.forename: Yanru
authors.initials: Y
authors.lastname: Qin
authors.forename: Ying-Hui
authors.initials: YH
authors.lastname: Zhu
authors.forename: Li
authors.initials: L
authors.lastname: Fu
authors.forename: Xin-Yuan
authors.initials: XY
authors.lastname: Guan
mesh_terms: D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D002465:Cell Movement; D049109:Cell Proliferation; D051358:Cyclin-Dependent Kinase 4 / Q000235:genetics; D015536:Down-Regulation; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D011379:Prognosis; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics; D016601:RNA-Binding Proteins / Q000235:genetics*; D015534:Trans-Activators / Q000235:genetics*
chemical_list: C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc; C405932:RBMS3 protein, human; D016601:RNA-Binding Proteins; D015534:Trans-Activators; C495900:CDK4 protein, human; D051358:Cyclin-Dependent Kinase 4