title: C/EBPα-induced miR-100 expression suppresses tumor metastasis and growth by targeting ZBTB7A in gastric cancer.
abstract: MicroRNAs have been reported to play key roles in various human cancers, including gastric cancer. However, understanding of the expression of miR-100 and its regulatory mechanisms in human gastric cancer remains elusive. In this study, we reveal that miR-100 is downregulated in gastric cancer samples and gastric cancer cell lines. Furthermore, lower miR-100 expression was found in primary gastric cancer samples with lymphatic metastasis compared to those without lymphatic metastasis. Overexpression of miR-100 suppressed tumor growth in vivo and inhibited gastric cancer invasion and metastasis in vitro and in vivo. Furthermore, we demonstrated that miR-100 reduced gastric cancer aggressiveness by directly targeting ZBTB7A. Knockdown of ZBTB7A by siRNA disrupted gastric cancer progression by impairing tumor invasion and metastasis. High expression of ZBTB7A was significantly correlated with poorer prognosis in gastric cancer patients. Our results also showed that the transcription factor CCAAT/enhancer-binding protein alpha (C/EBPα) could induce the expression of miR-100 by binding to the putative promoter region of miR-100. This study demonstrated that miR-100 could be induced by C/EBPα and may act as a tumor suppressor gene by inhibiting ZBTB7A.
authors.affiliation: Department of Pathology, Qilu Hospital, Shandong University, Jinan 250012, China.
authors.forename: Duan-Bo
authors.initials: DB
authors.lastname: Shi
authors.affiliation: Department of Pathology, Qilu Hospital, Shandong University, Jinan 250012, China.
authors.forename: Ya-Wen
authors.initials: YW
authors.lastname: Wang
authors.affiliation: Department of Pathology, Qilu Hospital, Shandong University, Jinan 250012, China.
authors.forename: Ai-Yan
authors.initials: AY
authors.lastname: Xing
authors.affiliation: Department of Pathology, Qilu Hospital, Shandong University, Jinan 250012, China.
authors.forename: Ji-Wei
authors.initials: JW
authors.lastname: Gao
authors.affiliation: Department of Pathology, Qilu Hospital, Shandong University, Jinan 250012, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Pathology, Qilu Hospital, Shandong University, Jinan 250012, China.
authors.forename: Xiang-Yu
authors.initials: XY
authors.lastname: Guo
authors.affiliation: Department of Pathology, Qilu Hospital, Shandong University, Jinan 250012, China. Electronic address: gaopeng@sdu.edu.cn.
authors.forename: Peng
authors.initials: P
authors.lastname: Gao
mesh_terms: D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D049109:Cell Proliferation; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009362:Neoplasm Metastasis; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014162:Transfection
chemical_list: D022762:CCAAT-Enhancer-Binding Proteins; C515848:CEBPA protein, human; D004268:DNA-Binding Proteins; D035683:MicroRNAs; D014157:Transcription Factors; C485514:ZBTB7A protein, human
keywords: C/EBPα; Gastric cancer; Metastasis; ZBTB7A; miR-100