title: Down-regulation of TCF21 by hypermethylation induces cell proliferation, migration and invasion in colorectal cancer.
abstract: Epigenetic alteration induced loss function of the transcription factor 21 (TCF21) has been associated with different types of human cancers. However, the epigenetic regulation and molecular functions of TCF21 in colorectal cancer (CRC) remain unknown. In this study, TCF21 expression levels and methylation status of its promoter region in CRC cell lines (n = 5) and CRC tissues (n = 151) as well as normal colorectal mucosa (n = 30) were assessed by RTq-PCR and methylation analysis (methylation specific PCR, MSP and bisulfite sequencing PCR, BSP), respectively. The cellular functions of TCF21 on CRC cell proliferation, apoptosis, invasion and migration were investigated in vitro. Our data revealed that TCF21 was frequently silenced by promoter hypermethylation in both tested CRC cell lines and primary CRC, and correlation analysis between methylation status and clinicopathologic parameters found that TCF21 methylation was significantly correlated with lymph node invasion (P = 0.013), while no significant correlation was found in other parameters. In addition, demethylation treatment resulted in re-expression of TCF21 in CRC cell lines, and cellular function experiments revealed that restoration of TCF21 inhibited CRC cell proliferation, promoted apoptosis and suppressed cell invasion and migration, suggesting that TCF21 may function as a tumor suppressor gene, which is downregulated through promoter hypermethylation in CRC development.
authors.affiliation: Department of Oncology, Xiangya Hospital Central South University, PR China.
authors.forename: Youyi
authors.initials: Y
authors.lastname: Dai
authors.affiliation: Department of Oncology, Hunan Provincial People's Hospital, PR China; The First Affiliated Hospital of Hunan Normal University, PR China.
authors.forename: Huaxin
authors.initials: H
authors.lastname: Duan
authors.affiliation: Cental Lab of Xiangya Hospital Central South University, PR China.
authors.forename: Chaojun
authors.initials: C
authors.lastname: Duan
authors.affiliation: Department of Oncology, Xiangya Hospital Central South University, PR China.
authors.forename: Rongrong
authors.initials: R
authors.lastname: Zhou
authors.affiliation: Department of Oncology, Xiangya Hospital Central South University, PR China.
authors.forename: Yuxiang
authors.initials: Y
authors.lastname: He
authors.affiliation: Department of Oncology, Xiangya Hospital Central South University, PR China.
authors.forename: Qingsong
authors.initials: Q
authors.lastname: Tu
authors.affiliation: Department of Oncology, Xiangya Hospital Central South University, PR China. Electronic address: 3153559525@qq.com.
authors.forename: Liangfang
authors.initials: L
authors.lastname: Shen
mesh_terms: D017209:Apoptosis / Q000235:genetics*; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics*; D049109:Cell Proliferation / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology*; D019175:DNA Methylation / Q000235:genetics; D015536:Down-Regulation; D044127:Epigenesis, Genetic / Q000235:genetics; D006801:Humans; D009361:Neoplasm Invasiveness; D011401:Promoter Regions, Genetic / Q000235:genetics
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; C491825:TCF21 protein, human
keywords: Cell invasion; Cell migration; Cell proliferation; Colorectal cancer; DNA methylation; Transcription factor 21 (TCF21)