miR-141-3p inhibits human stromal (mesenchymal) stem cell proliferation and differentiation
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miR-141-3p inhibits human stromal (mesenchymal) stem cell proliferation and differentiation. / Qiu, Weimin; Kassem, Moustapha.
I: BBA Molecular Cell Research, Bind 1843, Nr. 9, 09.2014, s. 2114-21.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - miR-141-3p inhibits human stromal (mesenchymal) stem cell proliferation and differentiation
AU - Qiu, Weimin
AU - Kassem, Moustapha
N1 - Copyright © 2014 Elsevier B.V. All rights reserved.
PY - 2014/9
Y1 - 2014/9
N2 - Wnt signaling determines human stromal (mesenchymal) stem cell (hMSC) differentiation fate into the osteoblast or adipocyte lineage. microRNAs (miRNAs) are small RNA molecules of 21-25 nucleotides that regulate many aspects of osteoblast biology. Thus, we examined miRNAs regulated by Wnt signaling in hMSC. We identified miRNA (miR)-141-3p as a Wnt target which in turn inhibited Wnt signaling. Moreover, miR-141-3p inhibited hMSC proliferation by arresting cells at the G1 phase of the cell cycle. miR-141-3p inhibited osteoblast differentiation of hMSC as evidenced by reduced alkaline phosphatase activity, gene expression and in vitro mineralized matrix formation. Bioinformatic studies, Western blot analysis and 3'UTR reporter assay demonstrated that cell division cycle 25A (CDC25A) is a direct target of miR-141-3p. siRNA-mediated knock-down of CDC25A inhibited hMSC proliferation and osteoblast differentiation. In summary, miR-141-3p acts as a negative regulator of hMSC proliferation and osteoblast differentiation. Targeting miR-141-3p could be used as an anabolic therapy of low bone mass diseases, e.g. osteoporosis.
AB - Wnt signaling determines human stromal (mesenchymal) stem cell (hMSC) differentiation fate into the osteoblast or adipocyte lineage. microRNAs (miRNAs) are small RNA molecules of 21-25 nucleotides that regulate many aspects of osteoblast biology. Thus, we examined miRNAs regulated by Wnt signaling in hMSC. We identified miRNA (miR)-141-3p as a Wnt target which in turn inhibited Wnt signaling. Moreover, miR-141-3p inhibited hMSC proliferation by arresting cells at the G1 phase of the cell cycle. miR-141-3p inhibited osteoblast differentiation of hMSC as evidenced by reduced alkaline phosphatase activity, gene expression and in vitro mineralized matrix formation. Bioinformatic studies, Western blot analysis and 3'UTR reporter assay demonstrated that cell division cycle 25A (CDC25A) is a direct target of miR-141-3p. siRNA-mediated knock-down of CDC25A inhibited hMSC proliferation and osteoblast differentiation. In summary, miR-141-3p acts as a negative regulator of hMSC proliferation and osteoblast differentiation. Targeting miR-141-3p could be used as an anabolic therapy of low bone mass diseases, e.g. osteoporosis.
KW - Animals
KW - Base Sequence
KW - Cell Differentiation
KW - Cell Proliferation
KW - G1 Phase Cell Cycle Checkpoints
KW - Gene Expression Regulation
KW - Gene Knockdown Techniques
KW - Humans
KW - Mesenchymal Stromal Cells
KW - Mice
KW - MicroRNAs
KW - Molecular Sequence Data
KW - Osteoblasts
KW - Wnt Signaling Pathway
KW - cdc25 Phosphatases
U2 - 10.1016/j.bbamcr.2014.06.004
DO - 10.1016/j.bbamcr.2014.06.004
M3 - Journal article
C2 - 24937190
VL - 1843
SP - 2114
EP - 2121
JO - B B A - Molecular Cell Research
JF - B B A - Molecular Cell Research
SN - 0167-4889
IS - 9
ER -
ID: 125959030