title: miR-210 regulates the interaction between pancreatic cancer cells and stellate cells.
abstract: There is accumulating evidence that pancreatic stellate cells (PSCs) promote the progression of pancreatic cancer. microRNAs (miRNAs) are small non-coding RNAs acting as negative regulators of gene expression at the post-transcriptional level. This study aimed to clarify the role of miRNAs in the interaction between PSCs and pancreatic cancer cells. Pancreatic cancer cells were mono-cultured or indirectly co-cultured with PSCs. miRNAs were prepared, and Agilent's miRNA microarray containing probes for 904 human miRNAs was used to identify differentially expressed miRNAs. miR-210 was identified as an upregulated miRNA by co-culture with PSCs. Conditioned media of PSCs activated ERK and Akt, but not hypoxia-inducible factor-1α pathway. PSCs-induced miR-210 upregulation was inhibited by inhibitors of ERK and PI3K/Akt pathways. Inhibition of miR-210 expression decreased migration, decreased the expression of vimentin and snai-1, and increased the membrane-associated expression of β-catenin in Panc-1 cells co-cultured with PSCs. In conclusion, our results suggest a novel role of miR-210 in the interaction between PSCs and pancreatic cancer cells.
authors.affiliation: Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Takikawa
authors.forename: Atsushi
authors.initials: A
authors.lastname: Masamune
authors.forename: Shin
authors.initials: S
authors.lastname: Hamada
authors.forename: Eriko
authors.initials: E
authors.lastname: Nakano
authors.forename: Naoki
authors.initials: N
authors.lastname: Yoshida
authors.forename: Tooru
authors.initials: T
authors.lastname: Shimosegawa
mesh_terms: D002450:Cell Communication / Q000235:genetics; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D018920:Coculture Techniques; D055785:Gene Knockdown Techniques; D006801:Humans; D000860:Hypoxia / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics*; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000473:pathology*; D058954:Pancreatic Stellate Cells / Q000166:cytology / Q000378:metabolism* / Q000473:pathology
chemical_list: C543800:MIRN210 microRNA, human; D035683:MicroRNAs
keywords: 4′, 6-diamidino-2-phenylinodole; 5-bromo-2′-deoxyuridine; BrdU; DAPI; EMT; Fibrosis; HIF; MicroRNA; OD; PSC-CM; PSCs; Pancreatic cancer; Pancreatitis; Stroma; conditioned medium of hPSC21-S/T cells; epithelial-mesenchymal transition; hypoxia-inducible factor; miRNA; micro RNA; optical density; pancreatic stellate cells