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The inhibitory effect of ZSCAN18 on proliferation in gastric cancer cells

ABSTRACT: Background: Zinc finger and scan domain containing 18 (ZSCAN18) belongs to zinc finger transcription factor superfamily, which consists of the hundreds of members that play critical roles in all steps of tumorigenesis. Although hypermethylation of ZSCAN18 promoter and its consequent deficiency in a variety of malignancies has been reported recently, its functions and mechanisms in the initiation and progression of gastric cancer (GC) are not clear. This study aims to investigate the roles of ZSCAN18 in gastric carcinogenesis. Methods: Methylation of ZSCAN18 promoter in GC cell lines were analyzed via MassARRAY and treatment of 5-Aza-2'-deoxycytidine. Bioinformatics analysis, qRT-PCR, western blot, immunohistochemistry, CCK-8, colony formation, and in vivo xenograft tumor model were used to examine the expression and function of ZSCAN18. Survival analysis was performed to determine the correlation between ZSCAN18 expression and prognosis of patients with GC. Genes modulated by ZSCAN18 in NCI-N87 cells were identified through RNA next generation sequence screening and further verified by qRT-PCR in AGS and NCI-N87 cells. Results: ZSCAN18 expression was markedly reduced in GC tissues as compared with that in adjacent normal tissues due to hypermethylation in GC. Likewise, ZSCAN18 expression was also significantly reduced in a panel of GC cell lines as the result of densely methylated ZSCAN18 promoter. Forced expression of ZSCAN18 inhibited proliferation in AGS and NCI-N87 cells in vitro. Additionally, ZSCAN18 impaired growth of NCI-N87 cells in immunodeficient mice. Survival analysis showed that ZSCAN18 expression was positively associated with favorable outcome in patients with GC. RNA next generation sequence screening showed three representative genes (FGF20, CEACAM5 and TP53INP2) involved in downstream signaling pathways modulated by ZSCAN18. Conclusions: Collectively, this study unveils the anti-cancer role of ZSCAN18 in GC, providing a promising diagnostic and therapeutic target.

ORGANISM(S): Homo sapiens

PROVIDER: GSE186232 | GEO | 2024/10/13

REPOSITORIES: GEO

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Project description:Aberrant DNA hypermethylation of CpG island (CGI) promoters are associated with transcriptional repression of many tumor suppressor genes and lead to tumor progression in many cancers. Most recently, one research group observed that aberrantly hypermethylated genes in multiple cancers are already repressed, but their promoters are maintained in a hypomethylated state in pre-cancerous tissues.Their studies didn't provide a clue to explain by what mechanisms those genes were repressed in pre-cancerous tissues. Another research group found that many genes with de novo promoter hypermethylation in colon cancer were among the subset of genes "bivalently" marked in embryonic stem cells and adult stem/progenitor cells by repressive Polycomb group proteins (PcG), which are known for maintaining low, but poised, transcription.These observations provide a clue that CGI promoter hypermethylation in cancers is associated with PcG target genes in pre-cancerous tissues.we took advantage of ChIP-BS-seq technology and applied it to examine H3K27me3 and H3K4me3 profiles for one normal lymphoblastoid cell line (YH) and three cancer cell lines including one cervical cancer cell line (Hela) and two gastric cancer (GC) cell lines (BGC-823 and AGS). We aplied ChIP-BS technology to examine H3K27me3 marks, which are catalyzed by the SET domain histone methyltransferase EZH2 and have a repressive function with 50bp pair-end sequencing. found H3K27me3 marks were enriched preferentially at CpG islands, (+/-500) transcription start sites (TSSs) and exons in two GC cell lines (BGC-823 and AGS). In YH cells, H3K27me3 marks were only preferentially enriched at CpG islands. In contrast, Hela cells presented a reverse pattern with highest H3K27me3 enrichment in intergenic regions. To confirm this result in Hela cells, we performed two independent replicates of ChIP-Seq and ChIP-BS-seq. Cause of useful was relative small. we still sequenced one 100bp pe reads replicate for H3K4me3 and two replicate for H3K27me3 ChIP-BS-seq.