Cross-validated Uncovery of a Diagnostic miRNA-mRNA Regulatory Hub in Osteoporosis
Bufan Li1, Jiaxing Zeng2, Mao-Lin He1*, Qifan Chen1*
1Department of Spinal Surgery, The First Affiliated Hospital of Guangxi Medical University, Shuangyong Road 6, Nanning, Guangxi Zhuang Autonomous Region, China, 530021
2Department of Traumatic Surgery & Microsurgery & Hand Surgery, Guangxi Zhuang Autonomous Region People's Hospital, Nanning, Guangxi Zhuang Autonomous Region,P.R. China, 530021
*Corresponding Authors: Qifan Chen and Mao-Lin He, Department of Spinal Surgery, The First Affiliated Hospital of Guangxi Medical University, Shuangyong Road 6, Nanning, Guangxi Zhuang Autonomous Region, China, 530021
https://doi.org/10.58624/SVOAOR.2026.06.009
Received: April 22, 2026
Published: May 19, 2026
Citation: Li B, Zeng J, He ML, Chen Q. Cross-validated Uncovery of a Diagnostic miRNA-mRNA Regulatory Hub in Osteoporosis. SVOA Orthopaedics 2026, 6:3, 60-73. doi: 10.58624/SVOAOR.2026.06.009
Abstract
Background: Osteoporosis is a complex skeletal disorder whose pathogenesis involves intricate transcriptional networks. Robust biomarker discovery and mechanistic elucidation remain challenging due to the prevalent use of single-dataset analyses in transcriptomics.
Methods: We integrated four independent datasets from the Gene Expression Omnibus (GEO) to construct a disease-specific miRNA-mRNA regulatory network. Our analytical pipeline included differential expression analysis, target prediction, rigorous cross-dataset validation, diagnostic efficacy assessment (ROC analysis), and in silico drug prediction.
Results: A core regulatory axis was identified, featuring downregulated hsa-miR-30b-5p and its upregulated targets, AP2A1 and CHST1. Additionally, four novel hub genes (PSMD5, GRB7, TRAF7, TTC7A) showed consistent dysregulation across datasets. All core genes exhibited exceptional diagnostic performance (AUC > 0.9).
Conclusions: Through multi-dataset validation, we delineated a novel molecular network in osteoporosis, encompassing a key miRNA-mRNA axis and previously unrecognized hub genes. This work provides a high-potential diagnostic biomarker panel and reveals new mechanistic targets for therapeutic development.
Keywords: Osteoporosis (OP); Core genes; Biomarkers; hsa-miR-30b-5p; AP2A1; CHST1