title: MeCP2 suppresses LIN28A expression via binding to its methylated-CpG islands in pancreatic cancer cells.
abstract: LIN28A aberrant expression contributes to the development of human malignancies. However, the LIN28A expression profile remains to be clarified. Herein, we report that LIN28A expression is directly associated with the methylation status of its two CpG island sites in pancreatic cancer cells. First, Bisulfite sequencing reveals that PANC1 cells possess the higher methylation rate at LIN28A CpG islands compared with SW1990 and PaTu8988 cells. Subsequently, LIN28A expression is increased at both mRNA and protein levels in pancreatic cancer cells treated with 5-Aza-2'-deoxycytidine (5-Aza-CdR), a DNA methyltransferase inhibitor. Further Chromatin immunoprecipitation (ChIP) assays indicate that methyl-CpG-binding protein 2 (MeCP2) binds preferentially to the two hypermethylated CpG islands sites at LIN28A promoter compare to MBD3. Expectedly, MeCP2 knockdown transcriptionally activates LIN28A expression in above cells, rather than MBD3 knockdown. Moreover, LIN28A overexpression remarkably improves OCT4, NANOG and SOX2 expression, and the ability of sphere and colony formation, and enhances the capacities of invasion in PaTu8988 and SW1990 cells, whereas LIN28A knockdown significantly inhibits the above malignant behaviors in PANC1 cells. These findings suggest that LIN28A is epigenetically regulated via MeCP2 binding to methylated-CpG islands, and may play a crucial role in pancreatic cancer progression.
authors.affiliation: Department of Gastroenterology, Affiliated Hospital of Jiangsu University, Jiangsu University, Zhenjiang, China.
authors.forename: Min
authors.initials: M
authors.lastname: Xu
authors.affiliation: Department of Gastroenterology, Affiliated Hospital of Jiangsu University, Jiangsu University, Zhenjiang, China.
authors.forename: Shihui
authors.initials: S
authors.lastname: Bian
authors.affiliation: Department of Gastroenterology, Affiliated Hospital of Jiangsu University, Jiangsu University, Zhenjiang, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Gastroenterology, Affiliated Hospital of Jiangsu University, Jiangsu University, Zhenjiang, China.
authors.forename: Junbo
authors.initials: J
authors.lastname: He
authors.affiliation: Department of Gastroenterology, Affiliated Hospital of Jiangsu University, Jiangsu University, Zhenjiang, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Gastroenterology, Affiliated Hospital of Jiangsu University, Jiangsu University, Zhenjiang, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Ge
authors.affiliation: Department of Gastroenterology, Affiliated Hospital of Jiangsu University, Jiangsu University, Zhenjiang, China.
authors.forename: Zhijun
authors.initials: Z
authors.lastname: Jiao
authors.affiliation: Department of Gastroenterology, Affiliated Hospital of Jiangsu University, Jiangsu University, Zhenjiang, China.
authors.forename: Youli
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Cell Biology, School of Medicine, Jiangsu University, Zhenjiang, China.
authors.forename: Wanxin
authors.initials: W
authors.lastname: Peng
authors.affiliation: Department of Cell Biology, School of Medicine, Jiangsu University, Zhenjiang, China.
authors.forename: Fengyi
authors.initials: F
authors.lastname: Du
authors.affiliation: Department of Pharmacology Toxicology and Cancer Institute, University of Mississippi Medical Center, Jackson, MS, USA.
authors.forename: Yinyuan
authors.initials: Y
authors.lastname: Mo
authors.affiliation: Department of Cell Biology, School of Medicine, Jiangsu University, Zhenjiang, China.
authors.forename: Aihua
authors.initials: A
authors.lastname: Gong
mesh_terms: D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D002465:Cell Movement; D049109:Cell Proliferation; D018899:CpG Islands; D019175:DNA Methylation; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D011401:Promoter Regions, Genetic; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D014408:Biomarkers, Tumor; C516326:LIN28B protein, human; C497392:MECP2 protein, human; D051783:Methyl-CpG-Binding Protein 2; D016601:RNA-Binding Proteins
keywords: CpG islands; LIN28A; MeCP2; pancreatic cancer