title: Inhibition of microRNA-21 via locked nucleic acid-anti-miR suppressed metastatic features of colorectal cancer cells through modulation of programmed cell death 4.
abstract: Colorectal cancer is among the most lethal of malignancies, due to its propensity to metastatic spread and multifactorial-chemoresistance. The latter property supports the need to identify novel therapeutic approaches for the treatment of colorectal cancer. MicroRNAs are endogenous non-coding small RNA molecules that function as post-transcriptional regulators of gene expression. Recently, programmed cell death 4 has been identified as a protein that increases during apoptosis. This gene is among the potential targets of miR-21 (OncomiR). Locked nucleic acid-modified oligonucleotides have recently emerged as a potential therapeutic option for targeting microRNAs. The aim of this study was to explore the functional role of locked nucleic acid-anti-miR-21 in the LS174T cell line in vitro and in vivo models. LS174T cells were treated with locked nucleic acid-anti-miR-21 for 24, 48, and 72 h in vitro. The expression of miR-21 and PDCD4 at messenger RNA (mRNA) level was evaluated by quantitative real-time polymerase chain reaction, while the protein level of PDCD4 was determined by Western blotting. Cell migratory behavior and the cluster-forming ability of cells were assessed before and after therapy. The disseminated tumor cells were assessed in the chick chorioallantoic membrane model by Alu quantitative polymerase chain reaction. Locked nucleic acid-anti-miR-21 was transfected successfully into the LS174T cells and inhibited the expression of miR-21. Locked nucleic acid-anti-miR-21 inhibited the migration and the number of cells forming clusters. Moreover, we found that locked nucleic acid-anti-miR-21 transfection was associated with a significant reduction in metastatic properties as assessed by the in ovo model. Our findings demonstrated the novel therapeutic potential of locked nucleic acid-anti-miR-21 in colon adenocarcinoma with high miR-21 expression.
authors.affiliation: 1 Department of Medical Biotechnology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.|2 Students Research Committee, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Reza
authors.initials: R
authors.lastname: Nedaeinia
authors.affiliation: 3 Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.
authors.forename: Mohammadreza
authors.initials: M
authors.lastname: Sharifi
authors.affiliation: 4 Molecular Medicine Group, Department of Modern Sciences and Technologies, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Amir
authors.initials: A
authors.lastname: Avan
authors.affiliation: 3 Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Kazemi
authors.affiliation: 5 Isfahan Research Center for Agriculture and Natural Resources, Isfahan, Iran.
authors.forename: Abdolreza
authors.initials: A
authors.lastname: Nabinejad
authors.affiliation: 6 Division of Medical Education, Brighton and Sussex Medical School, University of Brighton, Brighton, UK.
authors.forename: Gordon A
authors.initials: GA
authors.lastname: Ferns
authors.affiliation: 4 Molecular Medicine Group, Department of Modern Sciences and Technologies, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.|7 Biochemistry of Nutrition Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Majid
authors.initials: M
authors.lastname: Ghayour-Mobarhan
authors.affiliation: 3 Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.|8 Acquired Immunodeficiency Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.|9 Gerfa Namayesh Azmayesh (GENAZMA) Science and Research Institute, Isfahan, Iran.
authors.forename: Rasoul
authors.initials: R
authors.lastname: Salehi
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D002642:Chick Embryo; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D015316:Genetic Therapy; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control / Q000556:secondary; D035683:MicroRNAs / Q000037:antagonists & inhibitors* / Q000235:genetics* / Q000378:metabolism; D009362:Neoplasm Metastasis; D009841:Oligonucleotides / Q000008:administration & dosage / Q000235:genetics*; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D014162:Transfection
chemical_list: D051017:Apoptosis Regulatory Proteins; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; D009841:Oligonucleotides; C114487:PDCD4 protein, human; D016601:RNA-Binding Proteins; C477371:locked nucleic acid
keywords: PDCD4; colorectal cancer; locked nucleic acid-anti-microRNA; microRNA-21