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.
In order to better understand and elucidate the major determinants of red and white muscle phenotypic properties, the global gene expression profiling was performed in white (longissimus doris) and red (soleus) skeletal muscle of Chinese Meishan pigs using the Affymetrix Porcine Genechip. 550 transcripts at least 1.5-fold difference were identified at p < 0.05 level, with 323 showing increased expression and 227 decreased expression in red muscle. Quantitative real-time PCR validated the differential expression of eleven genes (α-Actin, ART3, GATA-6, HMOX1, HSP, MYBPH, OCA2, SLC12A4, TGFB1, TGFB3 and TNX). Twenty eight signaling pathways including ECM-receptor interaction, focal adhesion, TGF-beta signaling pathway, MAPK signaling pathway, Wnt signaling pathway, mTOR signaling pathway, insulin signaling pathway and cell cycle, were identified using KEGG pathway database. Our findings demonstrate previously unrecognized changes in gene transcription between red and white muscle, and some potential cascades identified in the study merit further investigation.
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