RRC ID 44439
Author Hashimoto Y, Akiyama Y, Yuasa Y.
Title Multiple-to-multiple relationships between microRNAs and target genes in gastric cancer.
Journal PLoS One
Abstract MicroRNAs (miRNAs) act as transcriptional regulators and play pivotal roles in carcinogenesis. According to miRNA target databases, one miRNA may regulate many genes as its targets, while one gene may be targeted by many miRNAs. These findings indicate that relationships between miRNAs and their targets may not be one-to-one. However, many reports have described only a one-to-one, one-to-multiple or multiple-to-one relationship between miRNA and its target gene in human cancers. Thus, it is necessary to determine whether or not a combination of some miRNAs would regulate multiple targets and be involved in carcinogenesis. To find some groups of miRNAs that may synergistically regulate their targets in human gastric cancer (GC), we re-analyzed our previous miRNA expression array data and found that 50 miRNAs were up-regulated on treatment with 5-aza-2'-deoxycytidine in a GC cell line. The "TargetScan" miRNA target database predicted that some of these miRNAs have common target genes. We also referred to the GEO database for expression of these common target genes in human GCs, which might be related to gastric carcinogenesis. In this study, we analyzed two miRNA combinations, miR-224 and -452, and miR-181c and -340. Over-expression of both miRNA combinations dramatically down-regulated their target genes, DPYSL2 and KRAS, and KRAS and MECP2, respectively. These miRNA combinations synergistically decreased cell proliferation upon transfection. Furthermore, we revealed that these miRNAs were down-regulated through promoter hypermethylation in GC cells. Thus, it is likely that the relationships between miRNAs and their targets are not one-to-one but multiple-to-multiple in GCs, and that these complex relationships may be related to gastric carcinogenesis.
Volume 8(5)
Pages e62589
Published 2013-1-1
DOI 10.1371/journal.pone.0062589
PII PONE-D-12-39468
PMID 23667495
PMC PMC3648557
MeSH Azacitidine / analogs & derivatives Carcinogenesis / genetics* Cell Line, Tumor Cell Proliferation DNA Methylation Decitabine Gene Expression Regulation, Neoplastic / genetics* Humans Intercellular Signaling Peptides and Proteins / genetics Intercellular Signaling Peptides and Proteins / metabolism Methyl-CpG-Binding Protein 2 / genetics Methyl-CpG-Binding Protein 2 / metabolism MicroRNAs / genetics* Nerve Tissue Proteins / genetics Nerve Tissue Proteins / metabolism Promoter Regions, Genetic / genetics Proto-Oncogene Proteins / genetics Proto-Oncogene Proteins / metabolism* Proto-Oncogene Proteins p21(ras) Stomach Neoplasms / genetics* Transfection ras Proteins / genetics ras Proteins / metabolism
IF 2.74
Times Cited 118
Human and Animal Cells MKN45(RCB1001) MKN74(RCB1002) TGBC11TKB(RCB1148) GCIY(RCB0555)