title: Human RGM249-derived small RNAs potentially regulate tumor malignancy.
abstract: The human noncoding RNA gene RGM249 has been shown to regulate the degree of cancer cell differentiation. In this study, we investigated the effects of 3 microRNA-like molecules digested from RGM249 on the loss of malignant properties in cancer cells in immunodeficient KSN/Slc mice. We utilized small interfering RNAs (siRNAs) alone or in combination with a cationized drug delivery system (DDS) consisting of atelocollagen or gelatin hydrogel microspheres. The results demonstrated growth inhibition and apoptosis and the inhibition of both neovascularization and metastasis, indicating that the DDSs effectively infiltrated the majority of tumor cells in vivo. Systemic administration of the 3 siRNAs inhibited the metastatic ability of malignant cells. Cotransfection of these siRNAs exerted a regulatory effect upon the genes involved in differentiation, pluripotency, and proliferation in cancer cells. These results suggest that RGM249-derived oligonucleotides may be involved in the regulation of metastasis, proliferation, and differentiation in vivo, and that the tested siRNAs may therefore represent a new anticancer therapeutic approach.
authors.affiliation: Division of Pharmacotherapeutics, Department of Pathophysiological and Therapeutic Science, Faculty of Medicine, Tottori University, Yonago, Tottori, Japan.
authors.forename: Norimasa
authors.initials: N
authors.lastname: Miura
authors.forename: Mika
authors.initials: M
authors.lastname: Shimizu
authors.forename: Waka
authors.initials: W
authors.lastname: Shinoda
authors.forename: Satoshi
authors.initials: S
authors.lastname: Tsuno
authors.forename: Reina
authors.initials: R
authors.lastname: Sato
authors.forename: Xinhui
authors.initials: X
authors.lastname: Wang
authors.forename: Jun-Ichiro
authors.initials: J
authors.lastname: Jo
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Tabata
authors.forename: Junichi
authors.initials: J
authors.lastname: Hasegawa
mesh_terms: D000818:Animals; D017209:Apoptosis; D001483:Base Sequence; D006528:Carcinoma, Hepatocellular / Q000098:blood supply / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D002454:Cell Differentiation; D049109:Cell Proliferation; D016503:Drug Delivery Systems; D015316:Genetic Therapy; D006801:Humans; D016867:Immunocompromised Host; D015552:Injections, Intralesional; D008113:Liver Neoplasms / Q000098:blood supply / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D008545:Melanoma / Q000098:blood supply / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D051379:Mice; D008819:Mice, Nude; D008969:Molecular Sequence Data; D009362:Neoplasm Metastasis / Q000517:prevention & control; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic; D009690:Nucleic Acid Conformation; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics* / Q000378:metabolism; D012878:Skin Neoplasms / Q000098:blood supply / Q000276:immunology / Q000473:pathology / Q000628:therapy*
chemical_list: D034741:RNA, Small Interfering