title: Development of microRNA-145 for therapeutic application in breast cancer.
abstract: MicroRNAs, small non-coding RNAs, are key regulators of tumorigenesis and cancer metastasis through inhibition of gene expression. Therefore, there is increasing interest in developing anti-cancer therapies using microRNAs. In this study, we determined the therapeutic potency of microRNA-145(miR-145) against breast cancer. We found a reverse-correlation between the expression of miR-145 and its target genes, such as fascin-1, c-myc, SMAD2/3 and IGF-1R in breast cancer cell lines and breast cancer patient tissues. Transfected miR-145 mimicking double-stranded oligonucleotides was directly reduced cell proliferation and motility via interaction with 3'UTR of target gene and also indirectly regulates Wnt signaling. An inhibitor of miR-145 nullified this decreasing effect of miR-145 on cell proliferation and motility. We prepared an adenoviral constructed miR-145(Ad-miR-145) and subjected it to breast cancer cells in vitro and orthotopic breast cancer mice in vivo. Ad-miR-145 suppressed cell growth and motility in both the in vitro and in vivo systems. Furthermore, a treatment combining Ad-miR-145 with 5-FU significantly showed anti-tumor effects, compared to treating alone. In conclusion, this study demonstrated that miR-145 suppresses tumor growth by inhibition of multiple tumor survival effectors, and more we suppose that miR-145 is potentially useful in the therapy of breast cancers.
authors: Gastric Cancer Branch, Division of Translational & Clinical Research I, National Cancer Center Research Institute and Hospital, Ilsandong-gu, Goyang-si, Gyeonggi-do, Republic of Korea.
authors: Seok-Jun
authors: SJ
authors: Kim
authors: Ji-Sun
authors: JS
authors: Oh
authors: Ji-Young
authors: JY
authors: Shin
authors: Kang-Duck
authors: KD
authors: Lee
authors: Ki Woong
authors: KW
authors: Sung
authors: Seok Jin
authors: SJ
authors: Nam
authors: Kyung-Hee
authors: KH
authors: Chun
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D015316:Genetic Therapy; D005822:Genetic Vectors; D057809:HEK293 Cells; D006801:Humans; D007150:Immunohistochemistry; D008325:Mammary Neoplasms, Experimental / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D051379:Mice; D035683:MicroRNAs / Q000008:administration & dosage / Q000235:genetics*; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D009368:Neoplasm Transplantation; D014162:Transfection
chemical_list: C541010:MIRN145 microRNA, human; D035683:MicroRNAs; D009363:Neoplasm Proteins