title: microRNA-125a-3p reduces cell proliferation and migration by targeting Fyn.
abstract: Fyn, a member of the Src family kinases (SFKs), has a pivotal role in cell adhesion, proliferation, migration and survival, and its overexpression is associated with several types of cancer. MicroRNAs (miRNAs) play a major role in post-transcriptional repression of protein expression. In light of the significant functions of Fyn, together with studies demonstrating miR-125a as a tumor-suppressing miRNA that is downregulated in several cancer cell types and on our bioinformatics studies presented here, we chose to examine the post-transcription regulation of Fyn by miR-125a-3p in the HEK 293T cell line. We show that Fyn expression can be dramatically reduced by elevated levels of miR-125a-3p. Following this reduction, the activity of proteins downstream of Fyn, such as FAK, paxillin and Akt (proteins known to be overexpressed in various tumors), is also reduced. On a broader level, we show that miR-125a-3p causes an arrest of the cell cycle at the G2/M stage and decreases cell viability and migration, probably in a Fyn-directed manner. The results are reinforced by control experiments conducted using Fyn siRNA and anti-miR-125a-3p, as well as by the fact that numerous cancer cell lines show a significant downregulation of Fyn after mir-125a-3p overexpression. Collectively, we conclude that miR-125a-3p has an important role in the regulation of Fyn expression and of its signaling pathway, which implies that it has a therapeutic potential in overexpressed Fyn-related diseases.
authors.affiliation: Department of Cell and Developmental Biology, Sackler Faculty of Medicine, Tel-Aviv University, Ramat-Aviv Tel-Aviv 69978, Israel.
authors.forename: Lihi
authors.initials: L
authors.lastname: Ninio-Many
authors.forename: Hadas
authors.initials: H
authors.lastname: Grossman
authors.forename: Noam
authors.initials: N
authors.lastname: Shomron
authors.forename: Dana
authors.initials: D
authors.lastname: Chuderland
authors.forename: Ruth
authors.initials: R
authors.lastname: Shalgi
mesh_terms: D059447:Cell Cycle Checkpoints / Q000235:genetics*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D019295:Computational Biology; D051417:Focal Adhesion Kinase 1 / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D017930:Genes, Reporter; D006801:Humans; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D016376:Oligonucleotides, Antisense / Q000235:genetics / Q000378:metabolism; D051419:Paxillin / Q000235:genetics / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D051076:Proto-Oncogene Proteins c-fyn / Q000235:genetics* / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
chemical_list: C531888:MIRN125 microRNA, human; D035683:MicroRNAs; D016376:Oligonucleotides, Antisense; C496061:PXN protein, human; D051419:Paxillin; D034741:RNA, Small Interfering; D008156:Luciferases; C494957:FYN protein, human; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human; D051076:Proto-Oncogene Proteins c-fyn; D051057:Proto-Oncogene Proteins c-akt
keywords: Fyn; Migration; Proliferation; miR-125a-3p; miRNA