title: CXCL12 methylation-mediated epigenetic regulation of gene expression in papillary thyroid carcinoma.
abstract: Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer, and its incidence rate is rapidly growing. It is necessary to understand the pathogenesis of PTC to develop effective diagnosis methods. Promoter methylation has been recognized to contribute to the alterations in gene expression observed in tumorigenesis. Our RNA-seq data identified 1191 differentially expressed mRNAs and 147 differentially expressed lncRNAs in PTC. Next, promoter methylation of these genes was detected by reduced representation bisulfite sequencing (RRBS) technology and comprehensively analyzed to identify differential methylation. In total, 14 genes (13 mRNAs and 1 lncRNA), in which methylation was intimately involved in regulating gene expression, were proposed as novel diagnostic biomarkers. To gain insights into the relationships among these 14 genes, a core co-function network was constructed based on co-expression, co-function and co-methylation data. Notably, CXCL12 was identified as an essential gene in the network that was closely connected with the other genes. These data suggested that CXCL12 down-regulation in PTC may be caused by promoter hypermethylation. Our study was the first to perform an RRBS analysis for PTC and suggested that CXCL12 may contribute to PTC development by methylation-mediated epigenetic regulation of gene expression.
authors.affiliation: Department of Endoerinology and Metabolism, The Second Affiliated Hospital, Harbin Medical University, Harbin 150001, China.
authors.forename: Sijia
authors.initials: S
authors.lastname: Zhang
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150081, China.
authors.forename: Yihan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Endoerinology and Metabolism, The Second Affiliated Hospital, Harbin Medical University, Harbin 150001, China.
authors.forename: Meijun
authors.initials: M
authors.lastname: Chen
authors.affiliation: Department of Endoerinology and Metabolism, The Second Affiliated Hospital, Harbin Medical University, Harbin 150001, China.
authors.forename: Lulu
authors.initials: L
authors.lastname: Sun
authors.affiliation: Department of Endoerinology and Metabolism, The Second Affiliated Hospital, Harbin Medical University, Harbin 150001, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Han
authors.affiliation: Department of Endoerinology and Metabolism, The Second Affiliated Hospital, Harbin Medical University, Harbin 150001, China.
authors.forename: V Kazakova
authors.initials: VK
authors.lastname: Elena
authors.affiliation: Department of Endoerinology and Metabolism, The Second Affiliated Hospital, Harbin Medical University, Harbin 150001, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Qiao
mesh_terms: D002291:Carcinoma, Papillary / Q000235:genetics*; D054377:Chemokine CXCL12 / Q000235:genetics*; D018899:CpG Islands; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D006801:Humans; D062085:RNA, Long Noncoding / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000235:genetics*; D059467:Transcriptome
chemical_list: C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D062085:RNA, Long Noncoding; D012333:RNA, Messenger