title: Epigenetically deregulated miR-200c is involved in a negative feedback loop with DNMT3a in gastric cancer cells.
abstract: Aberrant methylation of miRNAs is commonly observed in cancers. In the present study, we investigated the regulation of the miR-200 family and its role in regulating DNA methylation events in gastric cancer (GC). We demonstrated that miR‑200c was aberrantly expressed in GC and associated with histologic type and tumor progression. Hypermethylation of the promoter region was found to be responsible for the loss of miR-200c in GC cells. Demethylation agents led to recovery of miR-200c expression in GC cell lines. Moreover, DNMT3a knockdown abolished the hypermethylation of the miR-200c gene and induced upregulation of miR-200c expression, whereas ectopic DNMT3a expression increased miR-200c promoter methylation and decreased miR-200c expression. Conversely, transfection of miR-200c led to downregulation of DNMT3a protein and induced endogenous pre-miR-200c and pri-miR‑200c re-expression. Luciferase assays confirmed miR‑200c binding to the DNMT3a 3'UTR. Finally, ectopic expression of miR-200c or knockdown of DNMT3a expression impeded GC cell growth, migration and invasion. Taken together, these observations demonstrates a novel epigenetic feedback loop between miR-200c and DNMT3a in the carcinogenesis and progression of GC.
authors: Department of Gastroenterology and Hepatology, Guangzhou Digestive Diseases Center, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510180, P.R. China.
authors: Yingfei
authors: Y
authors: Li
authors: Department of Gastroenterology and Hepatology, Guangzhou Digestive Diseases Center, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510180, P.R. China.
authors: Yuqiang
authors: Y
authors: Nie
authors: Department of Hematology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510280, P.R. China.
authors: Sanfang
authors: S
authors: Tu
authors: Department of Gastroenterology and Hepatology, Guangzhou Digestive Diseases Center, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510180, P.R. China.
authors: Hong
authors: H
authors: Wang
authors: Department of Gastroenterology and Hepatology, Guangzhou Digestive Diseases Center, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510180, P.R. China.
authors: Yongjian
authors: Y
authors: Zhou
authors: Department of Gastroenterology and Hepatology, Guangzhou Digestive Diseases Center, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510180, P.R. China.
authors: Yanlei
authors: Y
authors: Du
authors: Department of General Surgery, Guangzhou Digestive Diseases Center, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510180, P.R. China.
authors: Jie
authors: J
authors: Cao
authors: Department of Gastroenterology and Hepatology, Guangzhou Digestive Diseases Center, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510180, P.R. China.
authors: Min
authors: M
authors: Ye
mesh_terms: D000328:Adult; D000368:Aged; D015153:Blotting, Western; D063646:Carcinogenesis / Q000235:genetics; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000096:biosynthesis* / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics*; D000090205:DNA Methyltransferase 3A; D015536:Down-Regulation; D044127:Epigenesis, Genetic / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000235:genetics; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic / Q000235:genetics; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
chemical_list: C000717967:DNMT3A protein, human; C533896:MIRN200 microRNA, human; D035683:MicroRNAs; D004248:DNA (Cytosine-5-)-Methyltransferases; D000090205:DNA Methyltransferase 3A