{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T08:16:44Z","timestamp":1789805804297,"version":"4.0.1"},"reference-count":38,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2021,10,26]],"date-time":"2021-10-26T00:00:00Z","timestamp":1635206400000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2021,10,26]],"date-time":"2021-10-26T00:00:00Z","timestamp":1635206400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AR068313"],"award-info":[{"award-number":["AR068313"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AR059810"],"award-info":[{"award-number":["AR059810"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000090","name":"Congressionally Directed Medical Research Programs","doi-asserted-by":"publisher","award":["PR162075"],"award-info":[{"award-number":["PR162075"]}],"id":[{"id":"10.13039\/100000090","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["16GRNT27760164"],"award-info":[{"award-number":["16GRNT27760164"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["11SDG5260033"],"award-info":[{"award-number":["11SDG5260033"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010551","name":"Texas Heart Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010551","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007144","name":"University of Houston","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007144","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Skeletal muscle atrophy is a debilitating complication of many chronic diseases, disuse conditions, and ageing. Genome\u2010wide gene expression analyses have identified that elevated levels of microRNAs encoded by the H19X locus are among the most significant changes in skeletal muscles in a wide scope of human cachectic conditions. We have previously reported that the H19X locus is important for the establishment of striated muscle fate during embryogenesis. However, the role of H19X\u2010encoded microRNAs in regulating skeletal mass in adults is unknown.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We have created a transgenic mouse strain in which ectopic expression of miR\u2010322\/miR\u2010503 is driven by the skeletal muscle\u2010specific muscle creatine kinase promoter. We also used an H19X mutant mouse strain in which transcription from the locus is interrupted by a gene trap. Animal phenotypes were analysed by standard histological methods. Underlying mechanisms were explored by using transcriptome profiling and validated in the two animal models and cultured myotubes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Our results demonstrate that the levels of H19X microRNAs are inversely related to postnatal skeletal muscle growth. Targeted overexpression of miR\u2010322\/miR\u2010503 impeded skeletal muscle growth. The weight of gastrocnemius muscles of transgenic mice was only 54.5% of the counterparts of wild\u2010type littermates. By contrast, interruption of transcription from the H19X locus stimulates postnatal muscle growth by 14.4\u201314.9% and attenuates the loss of skeletal muscle mass in response to starvation by 12.8\u201321.0%. Impeded muscle growth was not caused by impaired IGF1\/AKT\/mTOR signalling or a hyperactive ubiquitin\u2013proteasome system, instead accompanied by markedly dropped abundance of translation initiation factors in transgenic mice. miR\u2010322\/miR\u2010503 directly targets eIF4E, eIF4G1, eIF4B, eIF2B5, and eIF3M.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our study illustrates a novel pathway wherein H19X microRNAs regulate skeletal muscle growth and atrophy through regulating the abundance of translation initiation factors, thereby protein synthesis. The study highlights how translation initiation factors lie at the crux of multiple signalling pathways that control skeletal muscle mass.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jcsm.12827","type":"journal-article","created":{"date-parts":[[2021,10,27]],"date-time":"2021-10-27T01:58:15Z","timestamp":1635299895000},"page":"2174-2186","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["H19X\u2010encoded miR\u2010322(424)\/miR\u2010503 regulates muscle mass by targeting translation initiation factors"],"prefix":"10.1002","volume":"12","author":[{"given":"Rui","family":"Liang","sequence":"first","affiliation":[{"name":"Department of Biology and Biochemistry University of Houston  Houston TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaopeng","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Biology and Biochemistry University of Houston  Houston TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Biology and Biochemistry University of Houston  Houston TX USA"},{"name":"Department of Oncology The First Affiliated Hospital of Xi'an Jiaotong University  Xi'an Shaanxi Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Biology and Biochemistry University of Houston  Houston TX USA"},{"name":"Department of Oncology Shangluo Central Hospital  Shangluo Shaanxi Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex","family":"DesJarlais","sequence":"additional","affiliation":[{"name":"Department of Biology and Biochemistry University of Houston  Houston TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anam","family":"Syed","sequence":"additional","affiliation":[{"name":"Department of Biology and Biochemistry University of Houston  Houston TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raymond","family":"Saba","sequence":"additional","affiliation":[{"name":"Department of Biology and Biochemistry University of Houston  Houston TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi","family":"Tan","sequence":"additional","affiliation":[{"name":"Department of Experimental Therapeutics University of Texas MD Anderson Cancer Center  Houston TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Biology and Biochemistry University of Houston  Houston TX USA"},{"name":"Department of Oncology Shangluo Central Hospital  Shangluo Shaanxi Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuan","family":"Ji","sequence":"additional","affiliation":[{"name":"Department of Biology and Biochemistry University of Houston  Houston TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shreesti","family":"Shrestha","sequence":"additional","affiliation":[{"name":"Department of Biology and Biochemistry University of Houston  Houston TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinghong","family":"Ren","sequence":"additional","affiliation":[{"name":"Department of Oncology Shangluo Central Hospital  Shangluo Shaanxi Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Oncology The First Affiliated Hospital of Xi'an Jiaotong University  Xi'an Shaanxi Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoonjung","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Health and Human Performance University of Houston  Houston TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert J.","family":"Schwartz","sequence":"additional","affiliation":[{"name":"Department of Biology and Biochemistry University of Houston  Houston TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Soibam","sequence":"additional","affiliation":[{"name":"Department of Computer Science and Engineering Technology University of Houston\u2010Downtown  Houston TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bradley K.","family":"McConnell","sequence":"additional","affiliation":[{"name":"Department of Pharmacological &amp; Pharmaceutical Sciences University of Houston  Houston TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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