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Biosci. (Landmark Ed)"],"abstract":"<jats:p>Background: Skeletal muscle atrophy is a common musculoskeletal disorder that significantly reduces patient quality of life. Long non-coding RNA (lncRNA) XLOC_015548 has been identified as a pivotal regulator of C2C12 myoblast proliferation and differentiation. However, its role in mitigating denervation-induced muscle atrophy and the underlying mechanisms remain unclear. Methods: We employed lentiviral-mediated stable expression of XLOC_015548 in C2C12 myoblasts and skeletal muscle-specific XLOC_015548-edited mouse models to investigate the function of this lncRNA. Muscle atrophy models were established in vitro by glucocorticoid-induced atrophy with dexamethasone (DEX) and in vivo by sciatic nerve transection-induced denervation. The MEK inhibitor U0126 was used to assess the role of the growth arrest and DNA damage-inducible 45 gamma\/mitogen-activated protein kinase kinase\/extracellular signal-regulated kinase (Gadd45g\/MEK\/ERK) signaling pathway. Results: Overexpression of XLOC_015548 significantly activated the MEK\/ERK signaling pathway (p &lt; 0.05) by downregulating Gadd45g expression (p &lt; 0.05) and promoting its cytoplasmic localization, thereby enhancing cell proliferation and myotube formation. Furthermore, XLOC_015548 reduced the level of reactive oxygen species (ROS) (p &lt; 0.01), stabilized the mitochondrial membrane potential, and alleviated DEX-induced oxidative stress. These protective effects were partially reversed by U0126, confirming the involvement of the MEK\/ERK pathway. Skeletal muscle-specific overexpression of XLOC_015548 in vivo significantly reduced denervation-induced muscle atrophy (q &lt; 0.05) and increased the muscle fiber cross-sectional area. Conclusion: XLOC_015548 plays a critical role in promoting myogenic differentiation and protecting against muscle atrophy by regulating Gadd45g expression, activating the MEK\/ERK signaling pathway, and reducing oxidative stress. These findings underscore the therapeutic potential of XLOC_015548 in skeletal muscle atrophy, and provide a foundation for lncRNA-based treatment strategies.<\/jats:p>","DOI":"10.31083\/fbl36233","type":"journal-article","created":{"date-parts":[[2025,4,30]],"date-time":"2025-04-30T06:17:28Z","timestamp":1745993848000},"source":"Crossref","is-referenced-by-count":2,"title":["XLOC_015548 Mitigates Skeletal Muscle Atrophy via the Gadd45g\/MEK\/ERK Pathway and Redox Regulation"],"prefix":"10.31083","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7521-9168","authenticated-orcid":true,"given":"Tiantian","family":"Qi","sequence":"first","affiliation":[{"name":"Department of Bone & Joint Surgery, Peking University Shenzhen Hospital, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, 518036 Shenzhen, Guangdong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8898-921X","authenticated-orcid":true,"given":"Haotian","family":"Qin","sequence":"first","affiliation":[{"name":"Department of Bone & Joint Surgery, Peking University Shenzhen Hospital, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, 518036 Shenzhen, Guangdong, China"},{"name":"National & Local Joint Engineering Research Center of Orthopaedic Biomaterials, 518036 Shenzhen, Guangdong, China"},{"name":"Shenzhen Key Laboratory of Orthopaedic Diseases and Biomaterials Research, 518036 Shenzhen, Guangdong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5941-6452","authenticated-orcid":true,"given":"Fei","family":"Yu","sequence":"first","affiliation":[{"name":"Department of Spine Surgery, Shenzhen Second People\u2019s Hospital, The First Affiliated Hospital of Shenzhen University, 518035 Shenzhen, Guangdong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zimeng","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Bone & Joint Surgery, Peking University Shenzhen Hospital, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, 518036 Shenzhen, Guangdong, China"},{"name":"National & Local Joint Engineering Research Center of Orthopaedic Biomaterials, 518036 Shenzhen, Guangdong, China"},{"name":"Shenzhen Key Laboratory of Orthopaedic Diseases and Biomaterials Research, 518036 Shenzhen, Guangdong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yingqi","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Bone & Joint Surgery, Peking University Shenzhen Hospital, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, 518036 Shenzhen, Guangdong, China"},{"name":"National & Local Joint Engineering Research Center of Orthopaedic Biomaterials, 518036 Shenzhen, Guangdong, China"},{"name":"Shenzhen Key Laboratory of Orthopaedic Diseases and Biomaterials Research, 518036 Shenzhen, Guangdong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8002-9705","authenticated-orcid":true,"given":"Peng","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Bone & Joint Surgery, Peking University Shenzhen Hospital, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, 518036 Shenzhen, Guangdong, China"},{"name":"National & Local Joint Engineering Research Center of Orthopaedic Biomaterials, 518036 Shenzhen, Guangdong, China"},{"name":"Shenzhen Key Laboratory of Orthopaedic Diseases and Biomaterials Research, 518036 Shenzhen, Guangdong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hui","family":"Zeng","sequence":"first","affiliation":[{"name":"Department of Bone & Joint Surgery, Peking University Shenzhen Hospital, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, 518036 Shenzhen, Guangdong, China"},{"name":"National & Local Joint Engineering Research Center of Orthopaedic Biomaterials, 518036 Shenzhen, Guangdong, China"},{"name":"Shenzhen Key Laboratory of Orthopaedic Diseases and Biomaterials Research, 518036 Shenzhen, Guangdong, China"},{"name":"Department of Orthopedic Trauma, Shenzhen Second People\u2019s Hospital, The First Affiliated Hospital of Shenzhen University, 518035 Shenzhen, Guangdong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9262-4993","authenticated-orcid":true,"given":"Jian","family":"Weng","sequence":"first","affiliation":[{"name":"Department of Bone & Joint Surgery, Peking University Shenzhen Hospital, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, 518036 Shenzhen, Guangdong, 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