Developing a CeRNA-based LncRNA-miRNA-mRNA Regulatory Network to Uncover Roles in Skeletal Muscle Development

Overview

Journal Front Bioinform

Date 2025 Jan 30

PMID 39882307

Authors

Wang Wenlun

Yu Chaohang

Huang Yan

Li Wenbin

Zhou Nanqing

Hu Qianmin

Wu Shengcai

Yuan Qing

Yu Shirui

Zhang Feng

Zhu Lingyun

Affiliations

Soon will be listed here.

Abstract

The precise role of lncRNAs in skeletal muscle development and atrophy remain elusive. We conducted a bioinformatic analysis of 26 GEO datasets from mouse studies, encompassing embryonic development, postnatal growth, regeneration, cell proliferation, and differentiation, using R and relevant packages (limma et al.). LncRNA-miRNA relationships were predicted using miRcode and lncBaseV2, with miRNA-mRNA pairs identified via miRcode, miRDB, and Targetscan7. Based on the ceRNA theory, we constructed and visualized the lncRNA-miRNA-mRNA regulatory network using ggalluvial among other R packages. GO, Reactome, KEGG, and GSEA explored interactions in muscle development and regeneration. We identified five candidate lncRNAs (Xist, Gas5, Pvt1, Airn, and Meg3) as potential mediators in these processes and microgravity-induced muscle wasting. Additionally, we created a detailed lncRNA-miRNA-mRNA regulatory network, including interactions such as lncRNA Xist/miR-126/IRS1, lncRNA Xist/miR-486-5p/GAB2, lncRNA Pvt1/miR-148/RAB34, and lncRNA Gas5/miR-455-5p/SOCS3. Significant signaling pathway changes (PI3K/Akt, MAPK, NF-κB, cell cycle, AMPK, Hippo, and cAMP) were observed during muscle development, regeneration, and atrophy. Despite bioinformatics challenges, our research underscores the significant roles of lncRNAs in muscle protein synthesis, degradation, cell proliferation, differentiation, function, and metabolism under both normal and microgravity conditions. This study offers new insights into the molecular mechanisms governing skeletal muscle development and regeneration.

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