Integration analysis of lncRNA and mRNA expression data identifies DOCK4 as a potential biomarker for elderly osteoporosis

BMC Med Genomics. 2024 Mar 5;17(1):70. doi: 10.1186/s12920-024-01837-3.

Abstract

Background: We aimed to identify some potential biomarkers for elderly osteoporosis (OP) by integral analysis of lncRNA and mRNA expression data.

Methods: A total of 8 OP cases and 5 healthy participants were included in the study. Fasting peripheral venous blood samples were collected from individuals, and total RNA was extracted. RNA-seq library was prepared and sequenced on the Illumina HiSeq platform. Differential gene expression analysis was performed using "DESeq2" package in R language. Functional enrichment analysis was conducted using the "clusterProfiler" package, and the cis- and trans-regulatory relationships between lncRNA and target mRNA were analyzed by the lncTar software. A protein-protein interaction (PPI) network was constructed using the STRING database, and hub genes were identified through the MCODE plugin in Cytoscape.

Results: We identified 897 differentially expressed lncRNAs (DELs) and 1366 differentially expressed genes (DEGs) between normal and OP samples. After co-expression network analysis and cis-trans regulatory genes analysis, we identified 69 candidate genes regulated by lncRNAs. Then we further screened 7 genes after PPI analysis. The target gene DOCK4, trans-regulated by two lncRNAs, was found to be significantly upregulated in OP samples. Additionally, 4 miRNAs were identified as potential regulators of DOCK4. The potential diagnostic value of DOCK4 and its two trans-regulatory lncRNAs was supported by ROC analysis, indicating their potential as biomarkers for OP.

Conclusion: DOCK4 is a potential biomarker for elderly osteoporosis diagnostic. It is identified to be regulated by two lncRNAs and four miRNAs.

Keywords: DOCK4; Diagnostic; Elderly osteoporosis; lncRNA; miRNA.

MeSH terms

  • Aged
  • Biomarkers
  • Databases, Factual
  • GTPase-Activating Proteins
  • Humans
  • MicroRNAs*
  • Osteoporosis* / genetics
  • RNA, Long Noncoding* / genetics

Substances

  • RNA, Long Noncoding
  • MicroRNAs
  • Biomarkers
  • DOCK4 protein, human
  • GTPase-Activating Proteins