title: Locked nucleic acid-inhibitor of miR-205 decreases endometrial cancer cells proliferation in vitro and in vivo.
abstract: Pathogenesis of endometrial cancer has been connected with alterations of microRNA expression and in particular miR-205 up-regulation was consistently reported in this carcinoma. Presented study aimed to investigate if inhibition of miR-205 expression using LNA-modified-nucleotide would attenuate endometrial cancer cells proliferation in vitro and in vivo.In the course of the study we found that the proliferation of endometrial cancer cells (HEC-1-B, RL-95, KLE, Ishikawa) transfected with LNA-miR-205-inhibitor and evaluated using real time cell monitoring as well as standard cell proliferation assay, was significantly decreased. Next, LNA-miR-205-inhibitor was used to assess the in vivo effects of miR-205 inhibition of endometrial cancer growth. Cby.Cg-Foxn1/cmdb mice bearing endometrial cancer xenografts were intraperitoneally injected with nine dosages of 25mg/kg of miR-205-LNA-inhibitor or scramble control or phosphatase buffered saline and were observed for 32 days. We found that systemic administration of miR-205-LNA-inhibitor was technically possible, and exerted inhibitory effect on endometrial cancer xenograft growth in vivo with only mild toxic effects in treated animals.In conclusion our results suggest that systemic delivery of miR-205-LNA-inhibitor is feasible, devoid of significant toxicity, and could be a promising treatment strategy for endometrial cancer. Therefore it warrants further studies in other animal models.
authors.affiliation: Laboratory of Biostructure, Chair and Department of Human Anatomy, Medical University of Lublin, Jaczewskiego 4, 20-090, Lublin, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Torres
authors.affiliation: Laboratory of Biostructure, Chair and Department of Human Anatomy, Medical University of Lublin, Jaczewskiego 4, 20-090, Lublin, Poland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Kozak
authors.affiliation: Department of Clinical Pathomorphology, Medical University of Lublin, Jaczewskiego 8, 20-090, Lublin, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Korolczuk
authors.affiliation: Laboratory of Biostructure, Chair and Department of Human Anatomy, Medical University of Lublin, Jaczewskiego 4, 20-090, Lublin, Poland.
authors.forename: Dominika
authors.initials: D
authors.lastname: Rycak
authors.affiliation: Laboratory of Biostructure, Chair and Department of Human Anatomy, Medical University of Lublin, Jaczewskiego 4, 20-090, Lublin, Poland.
authors.forename: Paulina
authors.initials: P
authors.lastname: Wdowiak
authors.affiliation: Chair and Department of Human Anatomy, Medical University of Lublin, Jaczewskiego 4, 20-090, Lublin, Poland.
authors.forename: Ryszard
authors.initials: R
authors.lastname: Maciejewski
authors.affiliation: Chair and Department of Human Anatomy, Medical University of Lublin, Jaczewskiego 4, 20-090, Lublin, Poland.
authors.forename: Kamil
authors.initials: K
authors.lastname: Torres
mesh_terms: D000818:Animals; D001772:Blood Cell Count; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D004195:Disease Models, Animal; D016889:Endometrial Neoplasms / Q000235:genetics* / Q000473:pathology; D005260:Female; D015870:Gene Expression; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D009841:Oligonucleotides / Q000008:administration & dosage; D023041:Xenograft Model Antitumor Assays
chemical_list: D035683:MicroRNAs; D009841:Oligonucleotides; C534425:MIR205, human; C477371:locked nucleic acid
keywords: endometrial cancer; in vivo; locked nucleic acid; miR-205–LNA-inhibitor; mice xenograft