21
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      MicroRNA 107 Partly Inhibits Endothelial Progenitor Cells Differentiation via HIF-1β

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Endothelial progenitor cells (EPCs) play an important role in tissue repair after ischemic heart disease. In particular, the recovery of endothelial function is reliant on the ability and rate of EPCs differentiate into mature endothelial cells. The present study evaluated the effect of microRNA 107 (miR-107) on the mechanism of EPCs differentiation. EPCs were isolated from rats' bone marrow and miR-107 expression of EPCs in hypoxic and normoxic conditions were measured by real-time qualitative PCR. CD31 was analyzed by flow cytometry and eNOS was examined by real-time qualitative PCR and western blotting and these were used as markers of EPC differentiation. In order to reveal the mechanism, we used miR107 inhibitor and lentiviral vector expressing a short hairpin RNA (shRNA) that targets miR-107 and hypoxia-inducible factor-1 β (HIF-1β) to alter miR107 and HIF-1β expression. MiR-107 expression were increased in EPCs under hypoxic conditions. Up-regulation of miR-107 partly suppressed the EPCs differentiation induced in hypoxia, while down-regulation of miR-107 promoted EPC differentiation. HIF-1β was the target. This study indicated that miR-107 was up-regulated in hypoxia to prevent EPCs differentiation via its target HIF-1β. The physiological mechanisms of miR-107 must be evaluated if it is to be used as a potential anti-ischemia therapeutic regime.

          Related collections

          Most cited references21

          • Record: found
          • Abstract: found
          • Article: not found

          A microRNA signature of hypoxia.

          Recent research has identified critical roles for microRNAs in a large number of cellular processes, including tumorigenic transformation. While significant progress has been made towards understanding the mechanisms of gene regulation by microRNAs, much less is known about factors affecting the expression of these noncoding transcripts. Here, we demonstrate for the first time a functional link between hypoxia, a well-documented tumor microenvironment factor, and microRNA expression. Microarray-based expression profiles revealed that a specific spectrum of microRNAs (including miR-23, -24, -26, -27, -103, -107, -181, -210, and -213) is induced in response to low oxygen, at least some via a hypoxia-inducible-factor-dependent mechanism. Select members of this group (miR-26, -107, and -210) decrease proapoptotic signaling in a hypoxic environment, suggesting an impact of these transcripts on tumor formation. Interestingly, the vast majority of hypoxia-induced microRNAs are also overexpressed in a variety of human tumors.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Transplantation of ex vivo expanded endothelial progenitor cells for therapeutic neovascularization.

            Animal studies and preliminary results in humans suggest that lower extremity and myocardial ischemia can be attenuated by treatment with angiogenic cytokines. The resident population of endothelial cells that is competent to respond to an available level of angiogenic growth factors, however, may potentially limit the extent to which cytokine supplementation enhances tissue neovascularization. Accordingly, we transplanted human endothelial progenitor cells (hEPCs) to athymic nude mice with hindlimb ischemia. Blood flow recovery and capillary density in the ischemic hindlimb were markedly improved, and the rate of limb loss was significantly reduced. Ex vivo expanded hEPCs may thus have utility as a "supply-side" strategy for therapeutic neovascularization.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              P53-induced microRNA-107 inhibits HIF-1 and tumor angiogenesis.

              The pathway involving the tumor suppressor gene TP53 can regulate tumor angiogenesis by unclear mechanisms. Here we show that p53 regulates hypoxic signaling through the transcriptional regulation of microRNA-107 (miR-107). We found that miR-107 is a microRNA expressed by human colon cancer specimens and regulated by p53. miR-107 decreases hypoxia signaling by suppressing expression of hypoxia inducible factor-1beta (HIF-1beta). Knockdown of endogenous miR-107 enhances HIF-1beta expression and hypoxic signaling in human colon cancer cells. Conversely, overexpression of miR-107 inhibits HIF-1beta expression and hypoxic signaling. Furthermore, overexpression of miR-107 in tumor cells suppresses tumor angiogenesis, tumor growth, and tumor VEGF expression in mice. Finally, in human colon cancer specimens, expression of miR-107 is inversely associated with expression of HIF-1beta. Taken together these data suggest that miR-107 can mediate p53 regulation of hypoxic signaling and tumor angiogenesis.
                Bookmark

                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2012
                6 July 2012
                : 7
                : 7
                : e40323
                Affiliations
                [1 ]Department of Cardiology, School of Medicine, Shanghai Jiao-tong University, Xin-hua Hospital, Shanghai, China
                [2 ]Department of Cardiology, School of Medicine, Shanghai Jiao-tong University, No. 9 People's Hospital, Shanghai, China
                [3 ]Department of Laboratory Medicine, School of Medicine, Shanghai Jiao-tong University, No.9 People's Hospital, Shanghai, China
                [4 ]Department of Nuclear Medicine, School of Medicine, Tongji University, Shanghai 10th People's Hospital, Shangha, China
                Harvard Medical School, United States of America
                Author notes

                Conceived and designed the experiments: CW SM JC LW. Performed the experiments: CW SM JC ZP LW QZ YL. Analyzed the data: CW SM JC LW CS. Contributed reagents/materials/analysis tools: CW SM JC LW CS ZP. Wrote the paper: CW SM JC LW.

                Article
                PONE-D-12-09977
                10.1371/journal.pone.0040323
                3391260
                22792280
                94e23d70-67ec-403a-95cf-090d35420efd
                Meng et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
                History
                : 5 April 2012
                : 4 June 2012
                Page count
                Pages: 7
                Categories
                Research Article
                Biology
                Biochemistry
                Nucleic Acids
                RNA
                RNA interference
                Developmental Biology
                Cell Differentiation
                Genetics
                Epigenetics
                RNA interference
                Gene Expression
                RNA interference
                Medicine
                Anatomy and Physiology
                Immune Physiology
                Cell Surface Molecules
                Cardiovascular
                Atherosclerosis
                Coronary Artery Disease
                Valvular Disease
                Vascular Biology

                Uncategorized
                Uncategorized

                Comments

                Comment on this article