title: Basic Transcription Factor 3 Is Required for Proliferation and Epithelial-Mesenchymal Transition via Regulation of FOXM1 and JAK2/STAT3 Signaling in Gastric Cancer.
abstract: Gastric cancer (GC) is the most common epithelial malignancy worldwide. Basic transcription factor 3 (BTF3) plays a crucial role in the regulation of various biological processes. We designed experiments to investigate the molecular mechanism underlying the role of BTF3 in GC cell proliferation and metastasis. We confirmed that BTF3 expression was decreased in GC tissues and several GC cell lines. Lentivirus-mediated downregulation of BTF3 reduced cell proliferation, induced S and G2/M cell cycle arrest, and increased apoptosis. Knockdown of BTF3 significantly reduced the expression of Forkhead box M1 (FOXM1). Upregulation of FOXM1 significantly inhibited the decrease in cell proliferation due to BTF3 silencing, S and G2/M cell cycle arrest, and increase in apoptosis. Knockdown of BTF3 decreased Ki-67 and PCNA expression, whereas it increased p27 expression, which was inhibited by upregulation of FOXM1. Knockdown of BTF3 significantly decreased the ability to invade and migrate. Moreover, knockdown of BTF3 increased E-cadherin expression, whereas it decreased N-cadherin and ZEB2 expression, indicating a decrease in epithelial-mesenchymal transition (EMT). Phosphorylation of Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) was significantly inhibited by knockdown of BTF3. IL-6-stimulated phosphorylation of STAT3 and JAK2 markedly suppressed inhibition of EMT due to BTF3 silencing. Silencing of BTF3 decreased tumor volume and weight and reduced peritoneal nodules in implanted tumors. Our findings provide a novel understanding of the mechanism of GC and highlight the important role of BTF3/FOXM1 in tumor growth and BTF3/JAK2/STAT3 in EMT and metastasis.
authors.forename: De-Zhong
authors.initials: DZ
authors.lastname: Zhang
authors.forename: Bing-He
authors.initials: BH
authors.lastname: Chen
authors.forename: Lan-Fang
authors.initials: LF
authors.lastname: Zhang
authors.forename: Ming-Kun
authors.initials: MK
authors.lastname: Cheng
authors.forename: Xiang-Jie
authors.initials: XJ
authors.lastname: Fang
authors.forename: Xin-Jun
authors.initials: XJ
authors.lastname: Wu
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000502:physiology; D015536:Down-Regulation; D058750:Epithelial-Mesenchymal Transition; D000072278:Forkhead Box Protein M1 / Q000235:genetics / Q000378:metabolism*; D064593:Heterografts; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
chemical_list: C107585:FOXM1 protein, human; D000072278:Forkhead Box Protein M1; D009687:Nuclear Proteins; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D014157:Transcription Factors; C063552:transcription factor BTF3; C507924:JAK2 protein, human; D053614:Janus Kinase 2