title: MAPK and JAK/STAT pathways targeted by miR-23a and miR-23b in prostate cancer: computational and in vitro approaches.
abstract: The long-lasting inadequacy of existing treatments for prostate cancer has led to increasing efforts for developing novel therapies for this disease. MicroRNAs (miRNAs) are believed to have considerable therapeutic potential due to their role in regulating gene expression and cellular pathways. Identifying miRNAs that efficiently target genes and pathways is a key step in using these molecules for therapeutic purposes. Moreover, computational methods have been devised to help identify candidate miRNAs for each gene/pathway. MAPK and JAK/STAT pathways are known to have essential roles in cell proliferation and neoplastic transformation in different cancers including prostate cancer. Herein, we tried to identify miRNAs that target these pathways in the context of prostate cancer as therapeutic molecules. Genes involved in these pathways were analyzed with various algorithms to identify potentially targeting miRNAs. miR-23a and miR-23b were then selected as the best potential candidates that target a higher number of genes in these pathways with greater predictive scores. We then analyzed the expression of candidate miRNAs in LNCAP and PC3 cell lines as well as prostate cancer clinical samples. miR-23a and miR-23b showed a significant downregulation in cell line and tissue samples, a finding which is consistent with overactivation of these pathways in prostate cancer. In addition, we overexpressed miR-23a and miR-23b in LNCAP and PC3 cell lines, and these two miRNAs decreased IL-6R expression which has a critical role in these pathways. These results suggest the probability of utilizing miR-23a and miR-23b as therapeutic targets for the treatment of prostate cancer.
authors.affiliation: Molecular Medicine Department, Biotechnology Research Center, Pasteur Institute of Iran, No. 358, 12th Farwardin Ave, St, Tehran, Iran.
authors.forename: Seyed Hamid
authors.initials: SH
authors.lastname: Aghaee-Bakhtiari
authors.forename: Ehsan
authors.initials: E
authors.lastname: Arefian
authors.forename: Mahmood
authors.initials: M
authors.lastname: Naderi
authors.forename: Farshid
authors.initials: F
authors.lastname: Noorbakhsh
authors.forename: Vahideh
authors.initials: V
authors.lastname: Nodouzi
authors.forename: Mojgan
authors.initials: M
authors.lastname: Asgari
authors.forename: Pezhman
authors.initials: P
authors.lastname: Fard-Esfahani
authors.forename: Reza
authors.initials: R
authors.lastname: Mahdian
authors.forename: Masoud
authors.initials: M
authors.lastname: Soleimani
mesh_terms: D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D019295:Computational Biology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053612:Janus Kinases / Q000235:genetics; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D020929:Mitogen-Activated Protein Kinase Kinases / Q000235:genetics; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology; D050791:STAT Transcription Factors / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; C552430:MIRN23a microRNA, human; D035683:MicroRNAs; D050791:STAT Transcription Factors; D053612:Janus Kinases; D020929:Mitogen-Activated Protein Kinase Kinases