title: MicroRNA-34a modulates cytoskeletal dynamics through regulating RhoA/Rac1 cross-talk in chondroblasts.
abstract: MicroRNAs (miRNAs) have been implicated in various cellular processes, such as cell fate determination, cell death, and tumorigenesis. In the present study, we investigated the role of miRNA-34a (miR-34a) in the reorganization of the actin cytoskeleton, which is essential for chondrocyte differentiation. miRNA arrays to identify genes that appeared to be up-regulated or down-regulated during chondrogenesis were applied with chondrogenic progenitors treated with JNK inhibitor. PNA-based antisense oligonucleotides and miRNA precursor were used for investigation of the functional roles of miR-34a. We found that, in chick chondroprogenitors treated with JNK inhibitor, which suppresses chondrogenic differentiation, the expression levels of miR-34a and RhoA1 are up-regulated through modulation of Rac1 expression. Blockade of miR-34a via the use of PNA-based antisense oligonucleotides was associated with decreased protein expression of RhoA (a known modulator of stress fiber expression), down-regulation of stress fibers, up-regulation of Rac1, and recovery of protein level of type II collagen. miR-34a regulates RhoA/Rac1 cross-talk and negatively modulates reorganization of the actin cytoskeleton, which is one of the essential processes for establishing chondrocyte-specific morphology.
authors.affiliation: Department of Biological Sciences, College of Natural Sciences, Wonkwang University, Iksan, Chunbuk 570-749, Korea.
authors.forename: Dongkyun
authors.initials: D
authors.lastname: Kim
authors.forename: Jinsoo
authors.initials: J
authors.lastname: Song
authors.forename: Sunhyo
authors.initials: S
authors.lastname: Kim
authors.forename: Hyang Mi
authors.initials: HM
authors.lastname: Park
authors.forename: Churl-Hong
authors.initials: CH
authors.lastname: Chun
authors.forename: Jongkyung
authors.initials: J
authors.lastname: Sonn
authors.forename: Eun-Jung
authors.initials: EJ
authors.lastname: Jin
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D002642:Chick Embryo; D019902:Chondrocytes / Q000378:metabolism*; D020219:Chondrogenesis; D015870:Gene Expression; D005786:Gene Expression Regulation; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D008648:Mesoderm / Q000166:cytology; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D020239:Receptor Cross-Talk; D022502:Stress Fibers / Q000378:metabolism; D020830:rac1 GTP-Binding Protein / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: D035683:MicroRNAs; D047428:Protein Kinase Inhibitors; D048031:JNK Mitogen-Activated Protein Kinases; D020830:rac1 GTP-Binding Protein; D020742:rhoA GTP-Binding Protein