title: miR-30 family promotes migratory and invasive abilities in CD133(+) pancreatic cancer stem-like cells.
abstract: Pancreatic cancer is a deadly disease with a poor prognosis. Recently, miRNAs have been reported to be abnormally expressed in several cancers and play a role in cancer development and progression. However, the role of miRNA in cancer stem cells remains unclear. Therefore, our aim was to investigate the role of miRNA in the CD133(+) pancreatic cancer cell line Capan-1M9 because CD133 is a putative marker of pancreatic cancer stem cells. Using miRNA microarray, we found that the expression level of the miR-30 family decreased in CD133 genetic knockdown shCD133 Capan-1M9 cells. We focused on miR-30a, -30b, and -30c in the miR-30 family and created pancreatic cancer cell sublines, each transfected with these miRNAs. High expression of miR-30a, -30b, or -30c had no effect on cell proliferation and sphere forming. In contrast, these sublines were resistant to gemcitabine, which is a standard anticancer drug for pancreatic cancer, and in addition, promoted migration and invasion. Moreover, mesenchymal markers were up-regulated by these miRNAs, suggesting that mesenchymal phenotype is associated with an increase in migration and invasion. Thus, our study demonstrated that high expression of the miR-30 family modulated by CD133 promotes migratory and invasive abilities in CD133(+) pancreatic cancer cells. These findings suggest that targeted therapies to the miR-30 family contribute to the development of novel therapies for CD133(+) pancreatic cancer stem cells.
authors.affiliation: Division of Cancer and Regenerative Medicine, Frontier Biomedical Science and Swine Research Center, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima, 890-8520, Japan.
authors.forename: Koichiro
authors.initials: K
authors.lastname: Tsukasa
authors.affiliation: Division of Cancer and Regenerative Medicine, Frontier Biomedical Science and Swine Research Center, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima, 890-8520, Japan.|Keenan Research Centre of the Li Ka Shing Knowledge Institute of St. Michael's Hospital, Toronto, Canada.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Ding
authors.affiliation: Division of Cancer and Regenerative Medicine, Frontier Biomedical Science and Swine Research Center, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima, 890-8520, Japan.
authors.forename: Yumi
authors.initials: Y
authors.lastname: Miyazaki
authors.affiliation: Division of Cancer and Regenerative Medicine, Frontier Biomedical Science and Swine Research Center, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima, 890-8520, Japan.
authors.forename: Shyuichiro
authors.initials: S
authors.lastname: Matsubara
authors.affiliation: Department of Digestive Surgery, Breast and Thyroid Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima, 890-8520, Japan.
authors.forename: Shoji
authors.initials: S
authors.lastname: Natsugoe
authors.affiliation: Division of Cancer and Regenerative Medicine, Frontier Biomedical Science and Swine Research Center, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima, 890-8520, Japan. sonshin@m2.kufm.kagoshima-u.ac.jp.|Tanegashima Medical Center, 7463 Nishino-omote, Kagoshima, 891-3198, Japan. sonshin@m2.kufm.kagoshima-u.ac.jp.
authors.forename: Sonshin
authors.initials: S
authors.lastname: Takao
mesh_terms: D000071916:AC133 Antigen; D002465:Cell Movement / Q000235:genetics*; D002478:Cells, Cultured; D006801:Humans; D035683:MicroRNAs / Q000502:physiology*; D058990:Molecular Targeted Therapy; D009361:Neoplasm Invasiveness / Q000235:genetics; D014411:Neoplastic Stem Cells / Q000473:pathology*; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000473:pathology* / Q000628:therapy
chemical_list: D000071916:AC133 Antigen; C546086:MIRN30b microRNA, human; D035683:MicroRNAs; C000606023:PROM1 protein, human
keywords: CD133; Cancer stem cell; Invasion; Migration; Pancreatic cancer; miR-30 family; miRNA