title: MicroRNA-29a inhibits mesenchymal stem cell viability and proliferation by targeting Roundabout 1.
abstract: Secreted Slit glycoproteins and their Roundabout (Robo) receptors have been identified as important axon guidance molecules. The pivotal role of Slit‑Robo signaling is in regulating cell proliferation. MicroRNAs (miRNAs), a class of small non‑coding RNAs, function as critical regulators of gene expression by binding to the 3'‑untranslated region of mRNAs and causing mRNA degradation or translational repression. The present study demonstrated that downregulation of Robo1 using small interfering RNA inhibited mesenchymal stem cell (MSC) proliferation. Additionally, four miRNAs (miR), including miR‑218, miR‑29a, miR‑146 and miR‑148, inhibited the protein expression of Robo1 in the MSCs, with miR‑29 having the most marked effect. A luciferase reporter assay identified Robo1 as a novel target of miR‑29a. Overexpression of miR‑29a suppressed the protein expression levels of Robo1 and Slit2 and inhibited the viability and proliferation of the MSCs. By contrast, overexpression of Robo1 partly rescued these inhibitory effects of miR‑29a on the MSCs confirming that miR‑29a inhibited MSC viability and proliferation, at least partially, by directly targeting Robo1. These results indicated that the miR‑29a/Robo1 axis is crucial for the regulation of MSC viability and proliferation, suggesting that miR‑29a may serve as a potential clinical target for MSC expansion and stem cell transplantation.
authors.affiliation: Department of Cardiology, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, P.R. China.
authors.forename: Yudong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, P.R. China.
authors.forename: Shenghua
authors.initials: S
authors.lastname: Zhou
mesh_terms: D020413:3' Untranslated Regions; D049109:Cell Proliferation; D002470:Cell Survival; D015536:Down-Regulation; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000187:drug effects* / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D000097905:Roundabout Proteins; D000098552:Slit Homolog 2 Protein
chemical_list: D020413:3' Untranslated Regions; D036341:Intercellular Signaling Peptides and Proteins; D035683:MicroRNAs; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D011971:Receptors, Immunologic; D000097905:Roundabout Proteins; D000098552:Slit Homolog 2 Protein; C532045:MIRN29a microRNA, human