title: The Tumor Suppressor Roles of miR-433 and miR-127 in Gastric Cancer.
abstract: The discovery of microRNAs (miRNAs) provides a new and powerful tool for studying the mechanism, diagnosis and treatment of human cancers. Currently, the methylation epigenetic silencing of miRNAs with tumor suppressor features by CpG island hypermethylation is emerging as a common hallmark of different tumors. Here we showed that miR-433 and miR-127 were significantly down-regulated in gastric cancer (GC) tissues compared with the adjacent normal regions in 86 paired samples. Moreover, the lower level of miR-433 and miR-127 was associated with pM or pTNM stage in clinical gastric cancer patients. The restored expression of miR-433 and miR-127 in GC cells upon 5-Aza-CdR and TSA treatment suggested the loss of miR-433 and miR-127 was at least partly regulated by epigenetic modification in GC. Furthermore, the ectopic expression of miR-433 and miR-127 in gastric cancer cell lines HGC-27 inhibits cell proliferation, cell cycle progression, cell migration and invasion by directly interacting with the mRNA encoding oncogenic factors KRAS and MAPK4 respectively. Taken together, our results showed that miR-433 and miR-127 might act as tumor suppressors in GC, and it may provide novel diagnostic and therapeutic options for human GC clinical operation in the near future.
authors.affiliation: School of Computer and Information Technology, College of Life Sciences and Bioengineering, Beijing Jiaotong University, 3 Shangyuan Residence, Haidian District, Beijing 100044, China. lihuaguo@bjtu.edu.cn
authors.forename: Li-Hua
authors.initials: LH
authors.lastname: Guo
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
authors.forename: Jia
authors.initials: J
authors.lastname: Yu
authors.forename: Jin-Sheng
authors.initials: JS
authors.lastname: He
mesh_terms: D020413:3' Untranslated Regions; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001374:Azacitidine / Q000031:analogs & derivatives / Q000633:toxicity; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D000077209:Decitabine; D015536:Down-Regulation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D006877:Hydroxamic Acids / Q000633:toxicity; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D008875:Middle Aged; D009367:Neoplasm Staging; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D018631:ras Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; D006877:Hydroxamic Acids; C547276:MIRN127 microRNA, human; C548883:MIRN433 microRNA, human; D035683:MicroRNAs; C012589:trichostatin A; D000077209:Decitabine; D048049:Extracellular Signal-Regulated MAP Kinases; D018631:ras Proteins; D001374:Azacitidine