miR-210 regulates the interaction between pancreatic cancer cells and stellate cells

• Published in: Biochemical and biophysical research communications Vol. 437; no. 3; pp. 433 - 439
• Main Authors: Takikawa, Tetsuya, Masamune, Atsushi, Hamada, Shin, Nakano, Eriko, Yoshida, Naoki, Shimosegawa, Tooru
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 02.08.2013
• Subjects: Cell Communication - genetics; Cell Line, Tumor; Cell Transformation, Neoplastic - genetics; Coculture Techniques; Fibrosis; Gene Knockdown Techniques; Humans; Hypoxia - genetics; Hypoxia - metabolism; Hypoxia - pathology; MicroRNA; MicroRNAs - antagonists & inhibitors; MicroRNAs - biosynthesis; MicroRNAs - genetics; Pancreatic cancer; Pancreatic Neoplasms - genetics; Pancreatic Neoplasms - pathology; Pancreatic Stellate Cells - cytology; Pancreatic Stellate Cells - metabolism; Pancreatic Stellate Cells - pathology; Pancreatitis; Stroma; PSC-CM; HIF; Pancreatitis; Stroma; DAPI; EMT; MicroRNA; OD; PSCs; Pancreatic cancer; Fibrosis; miRNA; BrdU; pancreatic stellate cells; 5-bromo-2′-deoxyuridine; hypoxia-inducible factor; conditioned medium of hPSC21-S/T cells; 4′, 6-diamidino-2-phenylinodole; micro RNA; epithelial-mesenchymal transition; optical density
• DOI: 10.1016/j.bbrc.2013.06.097
• ISSN: 0006-291X

•Pancreatic stellate cells (PSCs) play a pivotal role in the progression of pancreatic cancer.•miR-210 was up-regulated in pancreatic cancer cells by co-culture with PSCs.•PSCs induced miR-210 expression through ERK- and PI3K/Akt-dependent pathways.•Inhibition of miR-210 expression decreased migration and epithelial-mesenchymal transition. 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.