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Long noncoding RNA Neat1 modulates myogenesis by recruiting Ezh2
Neat1 is widely expressed in many tissues and cells and exerts pro-proliferation effects on many cancer cells. However, little is known about the function of Neat1 in myogenesis. Here we characterized the roles of Neat1 in muscle cell formation and muscle regeneration. Gain- or loss-of-function stud...
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Published in: | Cell death & disease 2019-06, Vol.10 (7), p.505-15, Article 505 |
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Main Authors: | , , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | Neat1
is widely expressed in many tissues and cells and exerts pro-proliferation effects on many cancer cells. However, little is known about the function of
Neat1
in myogenesis. Here we characterized the roles of
Neat1
in muscle cell formation and muscle regeneration. Gain- or loss-of-function studies in C2C12 cells demonstrated that
Neat1
accelerates myoblast proliferation but suppresses myoblast differentiation and fusion. Further, knockdown of Neat1 in vivo increased the cross-sectional area of muscle fibers but impaired muscle regeneration. Mechanically,
Neat1
physically interacted with Ezh2 mainly through the core binding region (1001–1540 bp) and recruited Ezh2 to target gene promoters.
Neat1
promoted myoblast proliferation mainly by decreasing the expression of the cyclin-dependent kinase inhibitor
P21
gene but inhibited myoblast differentiation by suppressing the transcription of myogenic marker genes, such as
Myog
,
Myh4
, and
Tnni2
. Altogether, we uncover a previously unknown function of
Neat1
in muscle development and the molecular mechanism by which
Neat1
regulates myogenesis. |
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ISSN: | 2041-4889 2041-4889 |
DOI: | 10.1038/s41419-019-1742-7 |