lncRNA DLEU2 acts as a miR-181a sponge to regulate SEPP1 and inhibit skeletal muscle differentiation and regeneration
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Abstract
Abstract Background Sarcopenia is a serious public health problem. The ceRNA network has been demonstrated vital in the development of skeletal muscle, but there is currently no effective method to assess the risk of sarcopenia. The purpose of this research is to create and authenticate a ceRNA pathway based on a predictive model of sarcopenia. Methods A clinical prediction model for sarcopenia was established using the RNAs (validated by clinical data) that are co-differentially expressed in the database, and a ceRNA network was constructed. The correlation analysis of each element in the ceRNA network was performed according to the clinical samples and the GTEX database, and the possible key ceRNA pathways were screened. C2C12 mouse myoblast Cells experiments were used to verify these ceRNA pathways. Findings Based on four molecular markers of SEPP1, SV2A, GOT1 and GFOD1, we developed a new model for predicting sarcopenia with well accuracy, and constructed a ceRNA network accordingly. Clinical sample showed that the expression levels of lncDLEU2, SEPP1, and miR-181a were closely related to the risk of sarcopenia. The C2C12 mouse myoblast cells were cultivated to verify that lncDLEU2 inhibits muscle proliferation and differentiation by acting as a miR-181a sponge regulated SEPP1. Interpretation Our research developed a highly accurate prediction tool for the risk of sarcopenia. These findings suggest that lncDLEU2-miR-181a-SEPP1 pathway inhibits muscle differentiation and regeneration. This pathway may uncover some new therapeutic targets for the treatment of sarcopenia caused by aging.
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Fetuin-A induces a pro-inflammatory milieu by polarizing M1 macrophages in WAT, generating ROS and reducing insulin sensitivity, which combined with other pro-inflammatory cytokines causes the development of sarcopenia.
“Fetuin-A, a systemic calcification inhibitor, induces a pro-inflammatory milieu by polarizing M1 macrophages in WAT, generating ROS and reducing insulin sensitivity, which combined with other pro-inflammatory cytokines causes the development of sarcopenia [122,123,124,125].”
From Exerkines and Sarcopenia: Unveiling the Mechanism Behind Exercise-Induced Mitochondrial Homeostasis (2025) · cites this paper as [125]
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- Authors
- Wang, Y., Zhao, Z.-J., Kang, X.-R., Bian, T., Shen, Z.-M., Jiang, Y., Sun, B., Hu, H.-B., & Chen, Y.-S.
- Affiliations
- Shanghai Medical College of Fudan University (CN)
- Department of Neurosurgery, Shanghai Ninth People’s Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China
- Department of Otolaryngology-Head and Neck Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Ear Institute, Shanghai JiaoTong University School of Medicine, Shanghai Key Laboratory of Translational Medicine on Ear and Nose diseases, Shanghai, China
- Shanghai Jiao Tong University (CN)
- Department of General Surgery, Jinshan Hospital of Fundan University, Shanghai Medical College of Fudan University, Shanghai, China
- Jinshan Hospital of Fudan University (CN)
- Department of Surgery, Jinshan Hospital of Fundan University, Department of Orthopedics, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Venue
- Aging
- Publisher
- Impact Journals, LLC
- Published
- 2020-11-18
- Volume
- 12
- Issue
- 23
- Pages
- 24033-24056
- ISSN
- 1945-4589 (ISSN-L)
- PMC
- PMC7762514
- OpenAlex
- W3108902327
- Cited by
- 85
- References
- 78
- Citations by year
- 2026: 3 · 2025: 25 · 2024: 26 · 2023: 11 · 2022: 8 · 2021: 12
- FWCI
- 2.51
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Locations
- Aging (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Shanghai Jiao Tong University (ZH2018QNA19)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Health Sciences › Medicine › Physiology › Nutrition and Health in Aging
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
- Keywords
- sarcopenia, miR-181a, selenoprotein P, competing endogenous RNA, microRNA sponge, skeletal muscle differentiation, muscle regeneration, competing endogenous RNA network, molecular markers, C2C12 myoblasts, therapeutic target
- MeSH terms
- Aged, Aged, 80 and over, Animals, Cell Differentiation, Cell Line, Female, Humans, Male, Middle Aged, Regeneration, Signal Transduction, Muscle, Skeletal, Muscle Development, Databases, Genetic, MicroRNAs, Selenoprotein P, Mice, Gene Regulatory Networks, Sarcopenia, Transcriptome, RNA, Long Noncoding
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Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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