Lnc-ORA interacts with microRNA-532-3p and IGF2BP2 to inhibit skeletal muscle myogenesis

Abstract

Skeletal muscle is one of the most important organs of the animal body. Long noncoding RNAs play a crucial role in the regulation of skeletal muscle development via several mechanisms. We recently identified obesity-related lncRNA (lnc-ORA) in a search for long noncoding RNAs that influence adipogenesis, finding it impacted adipocyte differentiation by regulating the PI3K/protein kinase B/mammalian target of rapamycin pathway. However, whether lnc-ORA has additional roles, specifically in skeletal muscle myogenesis, is not known. Here, we found that lnc-ORA was significantly differentially expressed with age in mouse skeletal muscle tissue and predominantly located in the cytoplasm. Overexpression of lnc-ORA promoted C2C12 myoblast proliferation and inhibited myoblast differentiation. In contrast, lnc-ORA knockdown repressed myoblast proliferation and facilitated myoblast differentiation. Interestingly, silencing of lnc-ORA rescued dexamethasone-induced muscle atrophy in vitro. Furthermore, adeno-associated virus 9–mediated overexpression of lnc-ORA decreased muscle mass and the cross-sectional area of muscle fiber by upregulating the levels of muscle atrophy–related genes and downregulating the levels of myogenic differentiation–related genes in vivo. Mechanistically, lnc-ORA inhibited skeletal muscle myogenesis by acting as a sponge of miR-532-3p, which targets the phosphatase and tensin homolog gene; the resultant changes in phosphatase and tensin homolog suppressed the PI3K/protein kinase B signaling pathway. In addition, lnc-ORA interacted with insulin-like growth factor 2 mRNA-binding protein 2 and reduced the stability of myogenesis genes, such as myogenic differentiation 1 and myosin heavy chain. Collectively, these findings indicate that lnc-ORA could be a novel underlying regulator of skeletal muscle development. Skeletal muscle is one of the most important organs of the animal body. Long noncoding RNAs play a crucial role in the regulation of skeletal muscle development via several mechanisms. We recently identified obesity-related lncRNA (lnc-ORA) in a search for long noncoding RNAs that influence adipogenesis, finding it impacted adipocyte differentiation by regulating the PI3K/protein kinase B/mammalian target of rapamycin pathway. However, whether lnc-ORA has additional roles, specifically in skeletal muscle myogenesis, is not known. Here, we found that lnc-ORA was significantly differentially expressed with age in mouse skeletal muscle tissue and predominantly located in the cytoplasm. Overexpression of lnc-ORA promoted C2C12 myoblast proliferation and inhibited myoblast differentiation. In contrast, lnc-ORA knockdown repressed myoblast proliferation and facilitated myoblast differentiation. Interestingly, silencing of lnc-ORA rescued dexamethasone-induced muscle atrophy in vitro. Furthermore, adeno-associated virus 9–mediated overexpression of lnc-ORA decreased muscle mass and the cross-sectional area of muscle fiber by upregulating the levels of muscle atrophy–related genes and downregulating the levels of myogenic differentiation–related genes in vivo. Mechanistically, lnc-ORA inhibited skeletal muscle myogenesis by acting as a sponge of miR-532-3p, which targets the phosphatase and tensin homolog gene; the resultant changes in phosphatase and tensin homolog suppressed the PI3K/protein kinase B signaling pathway. In addition, lnc-ORA interacted with insulin-like growth factor 2 mRNA-binding protein 2 and reduced the stability of myogenesis genes, such as myogenic differentiation 1 and myosin heavy chain. Collectively, these findings indicate that lnc-ORA could be a novel underlying regulator of skeletal muscle development. Skeletal muscle development is regulated by a series of myogenic regulatory factors (MRFs) (1Braun T. Gautel M. Transcriptional mechanisms regulating skeletal muscle differentiation, growth and homeostasis.Nat. Rev. Mol. Cell. Biol. 2011; 12: 349-361Crossref PubMed Scopus (361) Google Scholar). The MRF family plays a crucial positive role in skeletal muscle myogenic determination and differentiation during embryogenesis and postnatal myogenesis and includes myogenic differentiation 1 (MyoD), myogenic factor 5, myogenin (MyoG), and myogenic regulatory factor 4 (2Buckingham M. Rigby P.W. Gene regulatory networks and transcriptional mechanisms that control myogenesis.Dev. Cell. 2014; 28: 225-238Abstract Full Text Full Text PDF PubMed Scopus (289) Google Scholar). Once MRFs have been activated, many myogenic transcription factors form obligate heterodimers with their coregulators to activate the myoblast differentiation program by regulating the transcription of many genes, including coding and noncoding genes. In addition, myoblast proliferation leads to an increase in the number of nuclei, contributing to muscle growth in some forms of muscle hypertrophy in adults. Skeletal muscle atrophy is controlled by the balance between the protein degradation rate and protein synthesis rate and induced by various stressors, including starvation, denervation, mechanical unloading, inflammation, and aging (3Schiaffino S. Dyar K.A. Ciciliot S. Blaauw B. Sandri M. Mechanisms regulating skeletal muscle growth and atrophy.FEBS J. 2013; 280: 4294-4314Crossref PubMed Scopus (667) Google Scholar). This balance reflects the physiological condition of the muscle fiber, and breakage results in muscular dystrophy (4Bonaldo P. Sandri M. Cellular and molecular mechanisms of muscle atrophy.Dis. Model Mech. 2013; 6: 25-39Crossref PubMed Scopus (598) Google Scholar). Two critical protein degradation pathways, the autophagic–lysosomal and ubiquitin–proteasome systems, are activated during skeletal muscle atrophy (5Jackman R.W. Cornwell E.W. Wu C.L. Kandarian S.C. Nuclear factor-kappaB signalling and transcriptional regulation in skeletal muscle atrophy.Exp. Physiol. 2013; 98: 19-24Crossref PubMed Scopus (44) Google Scholar, 6Jiao J. Demontis F. Skeletal muscle autophagy and its role in sarcopenia and organismal aging.Curr. Opin. Pharmacol. 2017; 34: 1-6Crossref PubMed Scopus (61) Google Scholar). These pathways include many atrophy-related genes, which are regulated by specific transcription factors. Muscle RING finger 1 (MuRF1) and muscle atrophy F-box (MAFbx) are atrophy markers, which represent two of many E3 ubiquitin ligases that are mostly expressed in skeletal muscle. Knockdown of MAFbx prevents skeletal muscle loss during fasting, and the absence of MuRF1 alleviates dexamethasone (Dex)-induced muscle atrophy in mice (7Bodine S.C. Baehr L.M. Skeletal muscle atrophy and the E3 ubiquitin ligases MuRF1 and MAFbx/atrogin-1.Am. J. Physiol. Endocrinol. Metab. 2014; 307: E469-484Crossref PubMed Scopus (416) Google Scholar). The PI3K/protein kinase B (AKT) signaling pathway is one of the signaling pathways that regulate mammalian skeletal muscle atrophy (8Wimmer R.J. Russell S.J. Schneider M.F. Green tea component EGCG, insulin and IGF-1 promote nuclear efflux of atrophy-associated transcription factor Foxo1 in skeletal muscle fibers.J. Nutr. Biochem. 2015; 26: 1559-1567Crossref PubMed Scopus (12) Google Scholar). The animal genome contains abundant noncoding RNAs, which serve as regulators of gene expression at the transcriptional, translational, and epigenetic levels. Noncoding RNAs regulate various muscle biological processes (9Jandura A. Krause H.M. The new RNA world: Growing evidence for long noncoding RNA functionality.Trends Genet. 2017; 33: 665-676Abstract Full Text Full Text PDF PubMed Scopus (121) Google Scholar, 10Cai R. Sun Y.M. Qimuge N.R. Wang G.Q. Wang Y. Chu G.Y. Yu T.Y. Yang G.S. Pang W.J. Adiponectin AS lncRNA inhibits adipogenesis by transferring from nucleus to cytoplasm and attenuating Adiponectin mRNA translation.Biochim. Biophys. Acta Mol. Cell Biol. Lipids. 2018; 1863: 420-432Crossref PubMed Scopus (37) Google Scholar, 11Pang W.J. Lin L.G. Xiong Y. Wei N. Wang Y. Shen Q.W. Yang G.S. Knockdown of PU.1 AS lncRNA inhibits adipogenesis through enhancing PU.1 mRNA translation.J. Cell. Biochem. 2013; 114: 2500-2512Crossref PubMed Scopus (62) Google Scholar). Recent studies have confirmed that functional long noncoding RNAs (lncRNAs) are involved in skeletal muscle development, including skeletal muscle cell proliferation, differentiation, injury, atrophy, and regeneration by chromatin remodeling, transcription regulation, and microRNA sponge absorption (12Wang S.S. Jin J.J. Xu Z.Y. Zuo B. Functions and regulatory mechanisms of lncRNAs in skeletal myogenesis, muscle disease and meat production.Cells. 2019; 8: 1107Crossref Scopus (11) Google Scholar, 13Geng T. Liu Y. Xu Y. Jiang Y. Zhang N. Wang Z. Carmichael G.G. Taylor H.S. Li D. Huang Y. H19 lncRNA promotes skeletal muscle insulin sensitivity in part by targeting AMPK.Diabetes. 2018; 67: 2183-2198Crossref PubMed Scopus (34) Google Scholar, 14Wang L. Zhao Y. Bao X. Zhu X. Kwok Y.K. Sun K. Chen X. Huang Y. Jauch R. Esteban M.A. LncRNA Dum interacts with Dnmts to regulate Dppa2 expression during myogenic differentiation and muscle regeneration.Cell Res. 2015; 25: 335-350Crossref PubMed Scopus (147) Google Scholar, 15Yu X. Zhang Y. Li T. Ma Z. Jia H. Chen Q. Zhao Y. Zhai L. Zhong R. Li C. Long non-coding RNA Linc-RAM enhances myogenic differentiation by interacting with MyoD.Nat. Commun. 2017; 8: 14016Crossref PubMed Scopus (83) Google Scholar, 16Zhou L. Sun K. Zhao Y. Zhang S. Wang X. Li Y. Lu L. Chen X. Chen F. Bao X. Linc-YY1 promotes myogenic differentiation and muscle regeneration through an interaction with the transcription factor YY1.Nat. Commun. 2015; 6: 10026Crossref PubMed Scopus (96) Google Scholar, 17Jin J.J. Lv W. Xia P. Xu Z.Y. Zheng A.D. Wang X.J. Wang S.S. Zeng R. Luo H.M. Li G.L. Zuo B. Long noncoding RNA SYISL regulates myogenesis by interacting with polycomb repressive complex 2.Proc. Natl. Acad. Sci. U. S. A. 2018; 115: E9802-9811Crossref PubMed Scopus (40) Google Scholar, 18Chen X. He L. Zhao Y. Li Y. Zhang S. Sun K. So K. Chen F. Zhou L. Lu L. Wang L. Zhu X. Bao X. Esteban M.A. Nakagawa S. et al.Malat1 regulates myogenic differentiation and muscle regeneration through modulating MyoD transcriptional activity.Cell Discov. 2017; 3: 17002Crossref PubMed Scopus (50) Google Scholar). Although the effects of these lncRNAs in skeletal muscle myogenesis have been partially characterized, the function and regulatory mechanism of obesity-related lncRNA (lnc-ORA) in this process remains elusive. In the present study, we found that lnc-ORA was significantly differentially expressed in skeletal muscle between two important developmental stages. Furthermore, the results indicated that lnc-ORA promoted myoblast proliferation, inhibited myoblast differentiation, and induced muscle atrophy in vitro. Moreover, overexpression of lnc-ORA reduced muscle mass and the cross-sectional area of muscle fibers by upregulating the levels of muscle atrophy–related genes and downregulating the levels of myoblast differentiation–related genes in vivo. Mechanistic investigations showed that lnc-ORA functioned as a sponge for and insulin-like growth factor 2 mRNA-binding protein 2 which activated phosphatase and tensin homolog and a critical pathway of myogenesis and muscle the findings a novel for the regulation of skeletal muscle development. whether lnc-ORA is with skeletal muscle development, the expression of lnc-ORA in the and from and mice was The results showed that the levels of lnc-ORA in mice in mice Furthermore, the of lnc-ORA was the at and decreased from to during myoblast proliferation The of lnc-ORA during the and decreased in the of C2C12 cell differentiation that lnc-ORA was involved in myoblast proliferation and differentiation during muscle the stability of lnc-ORA in C2C12 a was The results showed that the of lnc-ORA was that lnc-ORA is expressed in C2C12 In addition, genes, Gene and of and that lnc-ORA in the regulation of skeletal muscle development, muscle atrophy, muscle myoblast proliferation and differentiation indicated that lnc-ORA could regulate biological processes through the mammalian target of and signaling pathway Collectively, these results that lnc-ORA is a regulator of skeletal muscle development, through the signaling pathway. the role of lnc-ORA in myoblast proliferation, lnc-ORA overexpression and knockdown in C2C12 The results showed that overexpression and knockdown of lnc-ORA and Overexpression of lnc-ORA the number of and indicated that overexpression of lnc-ORA the number of that to and In addition, cell showed that overexpression of lnc-ORA the cell number Moreover, overexpression of lnc-ORA the mRNA and protein levels of genes, including and cell nuclear Furthermore, knockdown of lnc-ORA decreased the number of and the cell number the number of in and and the mRNA and protein levels of genes these results indicate that lnc-ORA promotes myoblast of lnc-ORA inhibits myoblast and of and in The of of and in results of mRNA levels of and knockdown of lnc-ORA of and of protein in represent the long obesity-related cell nuclear the of lnc-ORA myogenic differentiation, overexpression and knockdown during C2C12 cell differentiation. C2C12 induced by differentiation with the levels of lnc-ORA myogenic B and that overexpression and knockdown of lnc-ORA Overexpression of lnc-ORA decreased the number of myosin heavy the differentiation and the Moreover, overexpression of lnc-ORA the mRNA and protein levels of myogenic markers, including and knockdown of lnc-ORA the number of and the differentiation as as the at 4 myogenic 5, Knockdown of lnc-ORA the mRNA and protein levels of these 5, these results that lnc-ORA inhibits myogenic differentiation of of lnc-ORA promotes myogenic differentiation. of and 4 of differentiation knockdown of lnc-ORA The of the differentiation in of the in mRNA levels of myogenic genes 4 of differentiation knockdown of lnc-ORA of and of protein levels in represent the long obesity-related myosin heavy myogenic differentiation whether lnc-ORA could influence muscle atrophy, a muscle atrophy was in C2C12 The of lnc-ORA was significantly by the and an increase in the protein levels of MAFbx and MuRF1 and Furthermore, knockdown of lnc-ORA rescued muscle atrophy, as by Knockdown of lnc-ORA decreased the levels of MAFbx and MuRF1 and the levels of myogenic differentiation factors and knockdown of lnc-ORA rescued muscle atrophy in that lnc-ORA could be a target for muscle the role of lnc-ORA in the regulation of muscle development in mice with adeno-associated overexpression virus and with the control the showed decreased and mass of the and and the muscle of mice was showed that the cross-sectional of fibers in the in the and Overexpression of lnc-ORA significantly decreased the expression levels of and MyoD the expression levels of MAFbx and MuRF1 and The signaling pathway was inhibited in the of mice and these results that overexpression of lnc-ORA muscle mass and muscle atrophy in vivo. the molecular mechanism of lnc-ORA in myogenesis, to the of lnc-ORA in and The results showed that lnc-ORA was predominantly expressed in the cytoplasm of and and This finding that lnc-ORA plays a role in the regulation mechanism in the cytoplasm. Moreover, we that with a could be by lnc-ORA and and that as a target of this we and and The that to lnc-ORA and the and Furthermore, significantly and lnc-ORA through 2 RNA Moreover, lnc-ORA was significantly by with the control We have the number of the The results showed that the number of as that of lnc-ORA the we that lnc-ORA as a RNA to sponge Furthermore, promoted myogenic differentiation, as by of and indicated that the positive of lnc-ORA myoblast proliferation and it rescued the repressive of lnc-ORA myoblast differentiation and Moreover, showed the lnc-ORA the protein levels of and and In contrast, lnc-ORA knockdown reduced the protein of and the protein levels of and lnc-ORA inhibited myogenic differentiation and promoted muscle atrophy through absorption of via signaling as a for to control and of the and of the and The in of The in of and myogenic factors in represent the long obesity-related myosin heavy phosphatase and tensin the mechanism by which lnc-ORA regulates myogenesis, we a lnc-ORA to an RNA by mass this we identified an as to and we confirmed this interaction by was in C2C12 an was present in the at a in the control has been that could promote RNA We this to the RNA stability of The results showed that the interaction of lnc-ORA and lnc-ORA stability and the to sponge and Moreover, lnc-ORA to and regulated the stability of myogenesis genes such as MyoD and and we RNA to as an important of lnc-ORA in the myogenesis the we that acting as a sponge and interacting with to control inhibits skeletal muscle myogenesis and muscle atrophy regulatory mechanism of lnc-ORA that inhibits skeletal muscle myogenesis and muscle protein levels and the signaling pathway by as to sponge and with protein kinase insulin-like growth factor 2 mRNA-binding protein long obesity-related phosphatase and tensin Skeletal muscle is with physiological muscle and which influence of and animal meat several studies have indicated that lncRNAs are in skeletal muscle However, the and molecular mechanism of lnc-ORA myoblast proliferation, differentiation, and muscle atrophy are In the present study, we found that lnc-ORA was differentially expressed in mouse skeletal muscle with as a sponge and interacting with to myogenesis and muscle atrophy, and it could be a novel target for the regulation of skeletal muscle development. have been to regulate myoblast proliferation and differentiation, such as K. M. A. Y. A. H. H. H. K. lncRNA is for myogenic 2019; PubMed Scopus Google Wang J. Ma Yang D. Li H. Yang J. Huang Y. M. Ma Y. Chen H. promotes myoblast differentiation and muscle regeneration via 2018; PubMed Scopus Google M. D. L. L. A. T. C. M. A. long noncoding RNAs (lncRNAs) in lncRNA myoblast Cell. Biol. 2015; PubMed Scopus Google and Z. Zuo Liu Z. Chen J. Y. regulates the expression of long noncoding RNAs and to promote proliferation and of muscle 2018; PubMed Scopus Google Scholar). that knockdown of lnc-ORA inhibited proliferation and differentiation R. Zhang Q. Zhang Wei He C. Yang G.S. Pang W.J. novel is identified by and its knockdown inhibits adipogenesis by regulating the signaling 2019; 8: Google Scholar). In the study, we found that overexpression of lnc-ORA promoted myoblast proliferation inhibited Furthermore, its knockdown the that lnc-ORA is a regulatory factor of skeletal muscle number of studies have indicated that including Zhu Zheng M. Zhang muscle atrophy via family to activate 2019; PubMed Scopus Google Li J. D. C. Z. Liu J. Lu A. Zhang Zhang Long noncoding RNA skeletal muscle atrophy mechanical 2018; 26: Full Text Full Text PDF PubMed Scopus Google L. M. Liu X. Wang Y. S.S. H. Z. RNA promotes muscle in mice with 2018; PubMed Scopus Google L. F. C. F. P. B. C. C. A. L. S. cell the of the long non-coding RNA in the of muscle atrophy and Res. 2019; PubMed Scopus Google and C. M. K. L. F. The regulates expression and is a novel target for muscular 2017; Full Text Full Text PDF PubMed Scopus Google play a role in the regulation of muscle In the study, the of lnc-ORA in a muscle atrophy and knockdown of lnc-ORA significantly rescued muscle atrophy by MAFbx and MuRF1 and myogenic differentiation factor In addition, skeletal muscle atrophy is as a in skeletal muscle mass of muscle A. M. Muscle changes during Biol. 2018; PubMed Scopus Google Scholar, F. A. and muscle atrophy in J. 2019; 33: PubMed Scopus Google Scholar). Interestingly, we found that overexpression of lnc-ORA significantly decreased skeletal muscle mass and the cross-sectional area of muscle fibers in vivo. it is that lnc-ORA could be a target for muscle not regulate target genes at the transcriptional in the nucleus at the in the that the of lncRNAs is to their regulatory mechanism J. A. M. and of Biol. 2017; PubMed Scopus Google Scholar, F. and of long noncoding 2018; Full Text Full Text PDF PubMed Scopus Google Scholar, A. M. S.S. Long noncoding RNA and new Res. 2017; PubMed Scopus Google Scholar). Here, we found that lnc-ORA is in the nucleus and cytoplasm of the in the cytoplasm is that in the that lnc-ORA play an important role in lncRNAs function by to regulate the expression of target genes Zhou B. L. Wang H. Chu Xu Li Y. Chen Shen lncRNA promotes proliferation and differentiation of in skeletal muscle development by attenuating the function of J. 2018; PubMed Google Scholar, Li Sun Huang Chen H. The developmental of skeletal muscle a long noncoding promotes muscle differentiation by Biophys. Acta Mol. Cell Res. 1863: PubMed Scopus Google Scholar, M. D. T. M. A. long noncoding RNA muscle differentiation by as a 2011; Full Text Full Text PDF PubMed Scopus Google Scholar). showed that lnc-ORA as a RNA to which could target an important factor of myogenic genes, could regulate the signaling which has effects to promote myoblast differentiation in skeletal J. of signaling by Natl. Acad. Sci. U. S. A. PubMed Scopus Google Scholar). Furthermore, of the signaling pathway could activate the transcription factor family S. S. regulation of signaling in skeletal Cell. Endocrinol. 2013; PubMed Scopus Google Scholar, Yang H. S.C. inhibits the growth and effects of Physiol. PubMed Scopus (121) Google which the expression of the and MAFbx genes in the of muscle atrophy M. Sandri C. A. C. A. K. S. transcription factors the atrophy-related ubiquitin and skeletal muscle Full Text Full Text PDF PubMed Scopus Google Scholar, D. F. Y. M. The pathway prevents expression of muscle ubiquitin ligases by transcription Cell. Full Text Full Text PDF PubMed Scopus Google Scholar). we confirmed that lnc-ORA inhibited myogenic differentiation and muscle atrophy by from of In a is to and inhibits a number of target genes. a gene be by lnc-ORA could be to in some biological such as and Here, we confirmed that lnc-ORA as an sponge in skeletal muscle could promote the stability and of RNAs H. H. Sun W. X. H. Wu H. Zhao A. Liu C. C.L. S. R. X. et of RNA by enhances mRNA stability and Cell Biol. 2018; PubMed Scopus Google Scholar). Moreover, targets genes that are with muscle development X. Y. J. Yang Y. Chen Y. Z. F. the crucial role of in skeletal muscle Genet. PubMed Scopus Google Scholar). with the molecular mechanism of C. Li Z. K. Zhang Y. S. long non-coding regulates skeletal muscle differentiation by mRNA Cell. 2015; 34: Full Text Full Text PDF PubMed Scopus Google we found that lnc-ORA to and regulated the stability of myogenic genes such as MyoD and In we found that lnc-ORA as a sponge and interacts with to the signaling in the of myogenesis and of skeletal muscle we that lnc-ORA could be a novel underlying regulator of skeletal muscle development. mice from the of animal by of animal and of The C2C12 mouse myoblast cell was from with growth which was of and the to C2C12 cell differentiation was induced by differentiation of and myoblast proliferation, to for myogenic differentiation to with in with the The and and by The overexpression of lnc-ORA and lnc-ORA with the The was as a control muscle atrophy in C2C12 with and targeting lnc-ORA was The of lnc-ORA was to Y. Pang W.J. Wei N. Xiong Y. Wu W.J. Zhao Shen Q.W. Yang G.S. stability and expression of long non-coding 2014; PubMed Scopus (44) Google Scholar). In of lnc-ORA in and was with a with C2C12 with for the for with with for the specific of and at the with and a RNA from cell and tissue was by in with the synthesis was by transcription was with a the expression the specific of and gene for The was to was as a The of genes in this are in protein of the cell tissue was with was to R. Sun Y.M. Qimuge N.R. Wang G.Q. Wang Y. Chu G.Y. Yu T.Y. Yang G.S. Pang W.J. Adiponectin AS lncRNA inhibits adipogenesis by transferring from nucleus to cytoplasm and attenuating Adiponectin mRNA translation.Biochim. Biophys. Acta Mol. Cell Biol. Lipids. 2018; 1863: 420-432Crossref PubMed Scopus (37) Google Scholar). The the and MyoD MuRF1 MAFbx and cell nuclear The and The lnc-ORA by Y. Yu L. S. S. Chen W. Zhang X. W. Li J. Zhou R. Huang L. Y. L. Zhang L. Zhang L. targeting of the for J. 2017; PubMed Scopus Google Scholar). mice with mice in with virus including lnc-ORA control at and of to G.Q. Zhu L. Ma Chen Y. Yu T.Y. Yang G.S. Pang W.J. inhibits adipogenesis by of the signaling pathway in 2015; PubMed Scopus Google Scholar). and cell to M. Wang X. Chen X. R. Chen F. W. Yang Pang W. targeting and inhibits myogenesis through signaling Biol. 2017; PubMed Scopus Google Scholar). the C2C12 cell the with as as for the to The was as in R. Qimuge N.R. Ma Wang Zhang Q. Sun Y.M. Chen Yu T.Y. Yang G.S. Pang W.J. promotes myoblast proliferation and inhibits myoblast differentiation by targeting factor and Biol. 2018; Full Text Full Text PDF PubMed Scopus (12) Google Scholar). with and with for the with at 4 the with for 1 at and for The differentiation was as the of the nuclei, and the was as the of the nucleus number the to a S. R. of myoblast and muscle 2013; PubMed Scopus Google Scholar). and to target genes of is a functional for genes and genes of lnc-ORA with The are from which of networks of that gene The pathway for genes and genes of lnc-ORA is the The and of lnc-ORA and the of and was to M. Wang X. Chen X. R. Chen F. W. Yang Pang W. targeting and inhibits myogenesis through signaling Biol. 2017; PubMed Scopus Google Scholar). with control as as for the was the was to number of lnc-ORA and a of lnc-ORA and and via to the RNA from was and was as a in The to the of lnc-ORA and in to the was and in RNA and RNA and with the of protein was with of RNA for 1 at to and for 1 at the in for and the for mass the in C2C12 by and to The differentially expressed and by mass was as M. Y. Ma L. Wang X. X. Yang Li X. The long noncoding RNA to skeletal muscle myogenesis and the fiber Biol. Full Text Full Text PDF PubMed Scopus Google Scholar). C2C12 with in the and control to of was and induced myogenic differentiation at cell and with The was with and RNA was an The of lnc-ORA was through C2C12 to an of in in the and with to 2 the with and the RNA was from the The of RNA was a was to the of and and biological that at involved the of are as the of two by and of by with The of was by the two and was The to the findings of this are from the The that have of with the of this This contains R. C. and Q. Z. R. Y. and W. Y. R. Z. R. C. R. C. and W. P. and W. P. R. Z. W. P. and W. P. the This was by from the and and the and of

Topics & Concepts