Toward a novel muscle anabolic strategy for sarcopenia: Targeting the interaction between long noncoding RNA lncRNA-3 and MyoD1 promoter to promote myogenesis
Refereed conference paper presented and published in conference proceedings

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AbstractSarcopenia, age-related loss of skeletal muscle mass and strength, is associated with serious health consequences, but there is no clinically established therapy for sarcopenia to date. Here, we identified a sarcopenia-related lncRNA (lncRNA-3), which was significantly up-regulated in gastrocnemius muscle of aged sarcopenic mice (Figure 1). LncRNA-3 negatively regulated muscle mass and MyoD protein level in skeletal muscles of mice (Figure 2). Mechanistically, lncRNA-3 could interact with RbAp46/48, a subunit of Polycomb repressive complex 2 (PRC2), guide PRC2 to MyoD1 promoter, in turns catalyze the methylation of histone H3 at lysine 27 (H3K27) at MyoD1 promoter region and mediate MyoD1 gene silencing (Figure 3). Skeletal muscle-specific knockdown of lncRNA-3 promoted MyoD1 mRNA level and muscle mass in muscle-specific lncRNA-3 knockin mice (Figure 4). Low conservation in sequence limits the translation of lncRNA research. LncRNA3 was functionally conserved in human (lncRNA-3H), which was also interacted with PRC2 and MyoD1 promoter. LncRNA-3H knockdown promoted MyoD1 mRNA level and lncRNA-3H overexpression inhibited MyoD1 mRNA level in human skeletal muscle cells (Figure 5). To interfere with the interaction between lncRNA-3 and MyoD1, the MyoD1 promoter sequence was overexpressed in C2C12 cells and the skeletal muscle of aged mice. The cell differentiation of C2C12 cells was enhanced after MyoD1 promoter overexpression (Figure 6). Enhanced MyoD1 promoter expression in skeletal muscle suppressed the function of lncRNA-3 and counteract sarcopenia development in aged mice (Figure 7). The study uncovered the functional role of lncRNA-3 as an epigenetic regulator (Figure 8) and suggested the interaction between lncRNA-3 and MyoD1 promoter could be a potential therapeutic target to counteract sarcopenia development. It also provided a novel therapeutic strategy which to target the interaction between lncRNA and its conserved target protein or gene to overcome the limitation of low conservation of lncRNAs.
All Author(s) ListZhang ZK, Zhuo Z, Zhang BT, Guan D, Lu A, Zhang G
Name of ConferenceAnnual Meeting of the American-Society-for-Bone-and Mineral Research
Start Date of Conference20/09/2019
End Date of Conference23/09/2019
Place of ConferenceOrlando
Country/Region of ConferenceUnited States of America
Volume Number34
Issue NumberSuppl 1
Pages278 - 278
LanguagesEnglish-United Kingdom

Last updated on 2020-27-10 at 00:05