Deregulation of hsa-miR-20b expression in TNF-α-induced premature senescence of human pulmonary microvascular endothelial cells

miRNAs are important regulators of cellular senescence yet the extent of their involvement remains to be investigated. We sought to identify miRNAs that are involved in cytokine-induced premature senescence (CIPS) in endothelial cells. CIPS was established in young human pulmonary microvascular endo...

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Main Authors: Wong, Pooi Fong, Jamal, J., Tong, K.L., Khor, E.S., Yeap, C.E., Jong, H.L., Lee, S.T., Mustafa, Mohd Rais, AbuBakar, Sazaly
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Published: Elsevier 2017
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author Wong, Pooi Fong
Jamal, J.
Tong, K.L.
Khor, E.S.
Yeap, C.E.
Jong, H.L.
Lee, S.T.
Mustafa, Mohd Rais
AbuBakar, Sazaly
author_facet Wong, Pooi Fong
Jamal, J.
Tong, K.L.
Khor, E.S.
Yeap, C.E.
Jong, H.L.
Lee, S.T.
Mustafa, Mohd Rais
AbuBakar, Sazaly
author_sort Wong, Pooi Fong
collection UM
description miRNAs are important regulators of cellular senescence yet the extent of their involvement remains to be investigated. We sought to identify miRNAs that are involved in cytokine-induced premature senescence (CIPS) in endothelial cells. CIPS was established in young human pulmonary microvascular endothelial cells (HMVEC-Ls) following treatment with a sublethal dose (20 ng/ml) of tumor necrosis factor alpha (TNF-α) for 15 days. In parallel, HMVEC-Ls were grown and routinely passaged until the onset of replicative senescence (RS). Differential expression analysis following miRNA microarray profiling revealed an overlapped of eight deregulated miRNAs in both the miRNA profiles of RS and TNF-α-induced premature senescence cells. Amongst the deregulated miRNAs were members of the miR 17–92 cluster which are known regulators of angiogenesis. The role of hsa-miR-20b in TNF-α-induced premature senescence, a paralog member of the miR 17–92 cluster, was further investigated. Biotin-labeled hsa-miR-20b captured the enriched transcripts of retinoblastoma-like 1 (RBL1), indicating that RBL1 is a target of hsa-miR-20b. Knockdown of hsa-miR-20b attenuated premature senescence in the TNF-α-treated HMVEC-Ls as evidenced by increased cell proliferation, increased RBL1 mRNA expression level but decreased protein expression of p16INK4a, a cellular senescence marker. These findings provide an early insight into the role of hsa-miR-20b in endothelial senescence.
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spelling um.eprints-175452019-12-16T09:26:01Z http://eprints.um.edu.my/17545/ Deregulation of hsa-miR-20b expression in TNF-α-induced premature senescence of human pulmonary microvascular endothelial cells Wong, Pooi Fong Jamal, J. Tong, K.L. Khor, E.S. Yeap, C.E. Jong, H.L. Lee, S.T. Mustafa, Mohd Rais AbuBakar, Sazaly R Medicine RM Therapeutics. Pharmacology miRNAs are important regulators of cellular senescence yet the extent of their involvement remains to be investigated. We sought to identify miRNAs that are involved in cytokine-induced premature senescence (CIPS) in endothelial cells. CIPS was established in young human pulmonary microvascular endothelial cells (HMVEC-Ls) following treatment with a sublethal dose (20 ng/ml) of tumor necrosis factor alpha (TNF-α) for 15 days. In parallel, HMVEC-Ls were grown and routinely passaged until the onset of replicative senescence (RS). Differential expression analysis following miRNA microarray profiling revealed an overlapped of eight deregulated miRNAs in both the miRNA profiles of RS and TNF-α-induced premature senescence cells. Amongst the deregulated miRNAs were members of the miR 17–92 cluster which are known regulators of angiogenesis. The role of hsa-miR-20b in TNF-α-induced premature senescence, a paralog member of the miR 17–92 cluster, was further investigated. Biotin-labeled hsa-miR-20b captured the enriched transcripts of retinoblastoma-like 1 (RBL1), indicating that RBL1 is a target of hsa-miR-20b. Knockdown of hsa-miR-20b attenuated premature senescence in the TNF-α-treated HMVEC-Ls as evidenced by increased cell proliferation, increased RBL1 mRNA expression level but decreased protein expression of p16INK4a, a cellular senescence marker. These findings provide an early insight into the role of hsa-miR-20b in endothelial senescence. Elsevier 2017 Article PeerReviewed Wong, Pooi Fong and Jamal, J. and Tong, K.L. and Khor, E.S. and Yeap, C.E. and Jong, H.L. and Lee, S.T. and Mustafa, Mohd Rais and AbuBakar, Sazaly (2017) Deregulation of hsa-miR-20b expression in TNF-α-induced premature senescence of human pulmonary microvascular endothelial cells. Microvascular Research, 114. pp. 26-30. ISSN 0026-2862, DOI https://doi.org/10.1016/j.mvr.2017.06.002 <https://doi.org/10.1016/j.mvr.2017.06.002>. https://doi.org/10.1016/j.mvr.2017.06.002 DOI: 10.1016/j.mvr.2017.06.002
spellingShingle R Medicine
RM Therapeutics. Pharmacology
Wong, Pooi Fong
Jamal, J.
Tong, K.L.
Khor, E.S.
Yeap, C.E.
Jong, H.L.
Lee, S.T.
Mustafa, Mohd Rais
AbuBakar, Sazaly
Deregulation of hsa-miR-20b expression in TNF-α-induced premature senescence of human pulmonary microvascular endothelial cells
title Deregulation of hsa-miR-20b expression in TNF-α-induced premature senescence of human pulmonary microvascular endothelial cells
title_full Deregulation of hsa-miR-20b expression in TNF-α-induced premature senescence of human pulmonary microvascular endothelial cells
title_fullStr Deregulation of hsa-miR-20b expression in TNF-α-induced premature senescence of human pulmonary microvascular endothelial cells
title_full_unstemmed Deregulation of hsa-miR-20b expression in TNF-α-induced premature senescence of human pulmonary microvascular endothelial cells
title_short Deregulation of hsa-miR-20b expression in TNF-α-induced premature senescence of human pulmonary microvascular endothelial cells
title_sort deregulation of hsa mir 20b expression in tnf α induced premature senescence of human pulmonary microvascular endothelial cells
topic R Medicine
RM Therapeutics. Pharmacology
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