MicroRNA-146a Induces Lineage-Negative Bone Marrow Cell Apoptosis and Senescence by Targeting Polo-Like Kinase 2 Expression

Shanming Deng; Huilan Wang; Chunling Jia; Shoukang Zhu; Xianming Chu; Qi Ma; Jianqin Wei; Emily Chen; Wei Zhu; Conrad J Macon; Dushyantha T Jayaweera; Derek M Dykxhoorn; Chunming Dong

doi:10.1161/ATVBAHA.116.308378

Back

MicroRNA-146a Induces Lineage-Negative Bone Marrow Cell Apoptosis and Senescence by Targeting Polo-Like Kinase 2 Expression

Journal article

Open access

Peer reviewed

MicroRNA-146a Induces Lineage-Negative Bone Marrow Cell Apoptosis and Senescence by Targeting Polo-Like Kinase 2 Expression

Shanming Deng, Huilan Wang, Chunling Jia, Shoukang Zhu, Xianming Chu, Qi Ma, Jianqin Wei, Emily Chen, Wei Zhu, Conrad J Macon, …

Arteriosclerosis, thrombosis, and vascular biology, Vol.37(2), pp.280-290

2017-02

DOI: https://doi.org/10.1161/ATVBAHA.116.308378

PMID: 27908889

Abstract

Phosphorylation

Cell Proliferation

Age Factors

Apolipoproteins E - deficiency

Bone Marrow Cells - enzymology

Humans

Transcriptome

MicroRNAs - metabolism

Endothelial Progenitor Cells - enzymology

Transfection

RNA Interference

Cellular Senescence

HEK293 Cells

3' Untranslated Regions

Binding Sites

Protein-Serine-Threonine Kinases - metabolism

Signal Transduction

Down-Regulation

Mice, Inbred C57BL

Bone Marrow Cells - pathology

Protein-Serine-Threonine Kinases - genetics

Tumor Suppressor Protein p53 - metabolism

Genotype

Mice, Knockout

Cell Lineage

Phenotype

Animals

Endothelial Progenitor Cells - pathology

Apolipoproteins E - genetics

Cyclin-Dependent Kinase Inhibitor p16 - metabolism

MicroRNAs - genetics

Neovascularization, Physiologic

Apoptosis

Cell Movement

Lineage-negative bone marrow cells (lin- BMCs) are enriched in endothelial progenitor cells and mediate vascular repair. Aging-associated senescence and apoptosis result in reduced number and functionality of lin- BMCs, impairing their prorepair capacity. The molecular mechanisms underlying lin- BMC senescence and apoptosis are poorly understood. MicroRNAs (miRNAs) regulate many important biological processes. The identification of miRNA-mRNA networks that modulate the health and functionality of lin- BMCs is a critical step in understanding the process of vascular repair. The aim of this study was to characterize the role of the miR-146a-Polo-like kinase 2 (Plk2) network in regulating lin- BMC senescence, apoptosis, and their angiogenic capability. Transcriptome analysis in lin- BMCs isolated from young and aged wild-type and ApoE (apolipoprotein E) mice showed a significant age-associated increase in miR-146a expression. In silico analysis, expression study and Luciferase reporter assay established Plk2 as a direct target of miR-146a. miR-146a overexpression in young lin- BMCs inhibited Plk2 expression, resulting in increased senescence and apoptosis, via p16Ink4a/p19Arf and p53, respectively, as well as impaired angiogenic capacity in vitro and in vivo. Conversely, suppression of miR-146a in aged lin- BMCs increased Plk2 expression and rejuvenated lin- BMCs, resulting in decreased senescence and apoptosis, leading to improved angiogenesis. (1) miR-146a regulates lin- BMC senescence and apoptosis by suppressing Plk2 expression that, in turn, activates p16Ink4a/p19Arf and p53 and (2) modulation of miR-146a or its target Plk2 may represent a potential therapeutic intervention to improve lin- BMC-mediated angiogenesis and vascular repair.

Files and links (1)

url

https://doi.org/10.1161/ATVBAHA.116.308378View

Published (Version of record) Open

Metrics

6 Record Views

34 Times Cited - Web of Science

See more details

InCites Highlights

These are selected metrics from InCites Benchmarking & Analytics tool, related to this output

Collaboration types: Domestic collaboration; International collaboration
Citation topics: 1 Clinical & Life Sciences; 1.196 Micro & Long Noncoding RNA; 1.196.68 MicroRNAs
Web Of Science research areas: Hematology; Peripheral Vascular Disease
ESI research areas: Clinical Medicine

UN Sustainable Development Goals (SDGs)

This output has contributed to the advancement of the following goals:

Source: InCites

Details

Title: MicroRNA-146a Induces Lineage-Negative Bone Marrow Cell Apoptosis and Senescence by Targeting Polo-Like Kinase 2 Expression
Creators: Shanming Deng - From the Department of Medicine (S.D., H.W., C.J., S.Z., X.C., Q.M., J.W., E.C., W.Z., C.J.M., D.T.J, C.D.) and John T. Macdonald Foundation Department of Human Genetics (D.M.D.), Miller School of Medicine, University of Miami, FL; and Department of Cardiology, The Affiliated Hospital of Qingdao University, China (X.C.)
Huilan Wang - From the Department of Medicine (S.D., H.W., C.J., S.Z., X.C., Q.M., J.W., E.C., W.Z., C.J.M., D.T.J, C.D.) and John T. Macdonald Foundation Department of Human Genetics (D.M.D.), Miller School of Medicine, University of Miami, FL; and Department of Cardiology, The Affiliated Hospital of Qingdao University, China (X.C.)
Chunling Jia - From the Department of Medicine (S.D., H.W., C.J., S.Z., X.C., Q.M., J.W., E.C., W.Z., C.J.M., D.T.J, C.D.) and John T. Macdonald Foundation Department of Human Genetics (D.M.D.), Miller School of Medicine, University of Miami, FL; and Department of Cardiology, The Affiliated Hospital of Qingdao University, China (X.C.)
Shoukang Zhu - From the Department of Medicine (S.D., H.W., C.J., S.Z., X.C., Q.M., J.W., E.C., W.Z., C.J.M., D.T.J, C.D.) and John T. Macdonald Foundation Department of Human Genetics (D.M.D.), Miller School of Medicine, University of Miami, FL; and Department of Cardiology, The Affiliated Hospital of Qingdao University, China (X.C.)
Xianming Chu - From the Department of Medicine (S.D., H.W., C.J., S.Z., X.C., Q.M., J.W., E.C., W.Z., C.J.M., D.T.J, C.D.) and John T. Macdonald Foundation Department of Human Genetics (D.M.D.), Miller School of Medicine, University of Miami, FL; and Department of Cardiology, The Affiliated Hospital of Qingdao University, China (X.C.)
Qi Ma - From the Department of Medicine (S.D., H.W., C.J., S.Z., X.C., Q.M., J.W., E.C., W.Z., C.J.M., D.T.J, C.D.) and John T. Macdonald Foundation Department of Human Genetics (D.M.D.), Miller School of Medicine, University of Miami, FL; and Department of Cardiology, The Affiliated Hospital of Qingdao University, China (X.C.)
Jianqin Wei - From the Department of Medicine (S.D., H.W., C.J., S.Z., X.C., Q.M., J.W., E.C., W.Z., C.J.M., D.T.J, C.D.) and John T. Macdonald Foundation Department of Human Genetics (D.M.D.), Miller School of Medicine, University of Miami, FL; and Department of Cardiology, The Affiliated Hospital of Qingdao University, China (X.C.)
Emily Chen - From the Department of Medicine (S.D., H.W., C.J., S.Z., X.C., Q.M., J.W., E.C., W.Z., C.J.M., D.T.J, C.D.) and John T. Macdonald Foundation Department of Human Genetics (D.M.D.), Miller School of Medicine, University of Miami, FL; and Department of Cardiology, The Affiliated Hospital of Qingdao University, China (X.C.)
Wei Zhu - From the Department of Medicine (S.D., H.W., C.J., S.Z., X.C., Q.M., J.W., E.C., W.Z., C.J.M., D.T.J, C.D.) and John T. Macdonald Foundation Department of Human Genetics (D.M.D.), Miller School of Medicine, University of Miami, FL; and Department of Cardiology, The Affiliated Hospital of Qingdao University, China (X.C.)
Conrad J Macon - From the Department of Medicine (S.D., H.W., C.J., S.Z., X.C., Q.M., J.W., E.C., W.Z., C.J.M., D.T.J, C.D.) and John T. Macdonald Foundation Department of Human Genetics (D.M.D.), Miller School of Medicine, University of Miami, FL; and Department of Cardiology, The Affiliated Hospital of Qingdao University, China (X.C.)
Dushyantha T Jayaweera - From the Department of Medicine (S.D., H.W., C.J., S.Z., X.C., Q.M., J.W., E.C., W.Z., C.J.M., D.T.J, C.D.) and John T. Macdonald Foundation Department of Human Genetics (D.M.D.), Miller School of Medicine, University of Miami, FL; and Department of Cardiology, The Affiliated Hospital of Qingdao University, China (X.C.)
Derek M Dykxhoorn - From the Department of Medicine (S.D., H.W., C.J., S.Z., X.C., Q.M., J.W., E.C., W.Z., C.J.M., D.T.J, C.D.) and John T. Macdonald Foundation Department of Human Genetics (D.M.D.), Miller School of Medicine, University of Miami, FL; and Department of Cardiology, The Affiliated Hospital of Qingdao University, China (X.C.)
Chunming Dong - From the Department of Medicine (S.D., H.W., C.J., S.Z., X.C., Q.M., J.W., E.C., W.Z., C.J.M., D.T.J, C.D.) and John T. Macdonald Foundation Department of Human Genetics (D.M.D.), Miller School of Medicine, University of Miami, FL; and Department of Cardiology, The Affiliated Hospital of Qingdao University, China (X.C.). cdong3@med.miami.edu
Publication Details: Arteriosclerosis, thrombosis, and vascular biology, Vol.37(2), pp.280-290
Publisher: United States
Grant note: R01 AG041754 / NIA NIH HHS R21 AI116346 / NIAID NIH HHS
Academic Unit: Miller School of Medicine; Interdisciplinary Stem Cell Institute; John P. Hussman Institute for Human Genomics; UMMG Dept of Human Genetics (Dr. John T. Macdonald Foundation); UMMG Dept of Medicine - Infectious Diseases; UMMG Dept of Surgery - Div of Surgical Oncology
Language: English
Resource Type: Journal article
PMID: 27908889
Record Identifier: 991031576311202976