Sequencing-based analyses characterize a tumor suppressive role of mir-1271 repressed by DNA hypermethylation in gastric cancer. Homo sapiens

To identify tumor suppressive microRNAs repressed by DNA hypermethylation in gastric cancer (GC), we analyzed methylome and miRNome of EpCAM+/CD44+ GC cells. Among a set of microRNAs hypermethylated and downregulated in GC, mir-1271 was uncovered as a microRNA repressed by DNA hypermethylation in GC. Forced expression of mir-1271 significantly suppressed growth, migration, and invasion of GC cells both in vitro and in vivo. To identify target genes and cancer signaling pathways regulated by mir-1271, we examined differentially-expressed genes responsive to mir-1271 by performing RNA-sequencing. Overall design: 2 paired normal and GC cancer cells miRNA-seq, 3 GC cell lines MBD-seq, miR-1271 mimic treated GC cells and control cells RNA-seq

为鉴定胃癌（gastric cancer, GC）中受DNA高甲基化抑制的抑癌微RNA（microRNAs, miRNAs），本研究对EpCAM+/CD44+胃癌细胞的甲基化组（methylome）与微RNA转录组（miRNome）进行了分析。在胃癌中呈现高甲基化且表达下调的一系列微RNA中，mir-1271被鉴定为胃癌中受DNA高甲基化抑制的微RNA。过表达mir-1271可在体外与体内显著抑制胃癌细胞的增殖、迁移及侵袭能力。为鉴定mir-1271调控的靶基因与癌症信号通路，本研究通过RNA测序（RNA-sequencing）分析了响应mir-1271的差异表达基因。总体实验设计：2组配对的正常细胞与胃癌细胞的miRNA测序（miRNA-seq）、3种胃癌细胞系的甲基结合蛋白测序（MBD-seq）、经mir-1271模拟物处理的胃癌细胞及其对照细胞的RNA测序