RRC ID 68998
Author Xu J, Zhou Y, Yang J, Gu Y, Zhang E, Yuan W, Wang C, Jin G, Ma H, Hu Z.
Title Hypomethylation-activated cancer-testis gene LIN28B promotes cell proliferation and metastasis in gastric cancer.
Journal Gene
Abstract BACKGROUND:Previous studies have revealed the significance of several cancer/testis (CT) genes in gastric cancer (GC). Here, we identified candidate CT oncogenes in GC, which were activated by the promoter (p) hypomethylation.
METHODS:Transcriptome profiling and DNA methylation data of stomach adenocarcinoma (STAD) were downloaded from The Cancer Genome Atlas (TCGA) database. We applied multiple Cox regression analysis to identify survival-related CT genes. CpG sites associated with hypomethylated activation were defined by Spearman's rank correlation analysis. We used the CRISPR/dCas9 technique to accurately mediate p hypomethylation in a GC cell line (HGC27) and verify the effect of targeted CpG sites on gene expression. Finally, we verified the function via gain- and loss-of-function assays in vitro.
RESULTS:We recognized LIN28B as a highly activated CT gene in GC, whose high expression was associated with poor prognosis of GC patients [hazard ratio (HR) = 1.90, 95 %CI:1.26-2.87, P = 2.14 × 10-3]. Bioinformatics analysis found that hypomethylation of four CpG sites at LIN28B p were negatively correlated with its elevated expression, and we verified that p hypomethylation could activate LIN28B expression via accurately mediated p methylation. Moreover, knockout of LIN28B markedly repressed proliferation, metastasis, and invasion of GC cells in vitro. In contrast, LIN28B over-expression could promote metastasis and invasion of GC cells.
CONCLUSION:In summary, we found that CT gene LIN28B could be activated by p hypomethylation in GC, which suggested that hypomethylation of specific CpG sites could be a potential molecular marker for prognosis prediction and individualized treatment among GC patients.
Volume 813
Pages 146115
Published 2022-3-1
DOI 10.1016/j.gene.2021.146115
PII S0378-1119(21)00710-1
PMID 34902508
MeSH Adenocarcinoma / genetics Cell Line, Tumor Cell Proliferation / genetics CpG Islands / genetics DNA Methylation* Databases, Genetic Gene Expression Gene Expression Profiling / methods Humans Male Prognosis Promoter Regions, Genetic Proportional Hazards Models RNA-Binding Proteins / genetics* RNA-Binding Proteins / metabolism Stomach Neoplasms / genetics* Stomach Neoplasms / metabolism Stomach Neoplasms / pathology Testis / metabolism Transcriptional Activation Transcriptome
IF 2.984
Human and Animal Cells MKN1(RCB1003) MKN74(RCB1002)