Zhou Yong, Yu Shengyuan, Xue Bing, Zhang Xi, Gao Ming, Liu Yishu
The Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
Biochem Genet. 2025 May 13. doi: 10.1007/s10528-025-11131-1.
This study aimed to identify differentially expressed long non-coding RNAs (lncRNAs) and messenger RNAs (mRNAs) in damaged cartilage (DC) and un-damaged cartilage (UDC) in human osteoarthritis (OA), exploring their roles in disease progression through bioinformatics analysis and ceRNA network construction. Cartilage samples from 5 OA patients undergoing total knee arthroplasty were analyzed. RNA sequencing was used to detect the expression of lncRNAs and mRNAs in DC and UDC samples. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to investigate biological processes. A ceRNA network was constructed, and differentially expressed RNAs were validated by quantitative real-time polymerase chain reaction (qRT-PCR). In the damaged cartilage (DC) samples, 5 lncRNAs were significantly upregulated, and 15 were significantly downregulated, while 8 mRNAs were upregulated, and 8 were downregulated. The differential expression of lncRNAs, including LINC01411, AL596087.2, PCDH20, LRFN2, and AL583785.1, was confirmed using qRT-PCR, with p-values for all results showing statistical significance (p < 0.05). GO/KEGG enrichment analysis revealed key pathways such as Ras, PI3K-Akt, and MAPK that were significantly involved in OA pathogenesis. The ceRNA network construction highlighted crucial miRNA interactions, identifying potential regulators of cartilage-related biological processes. Differentially expressed lncRNAs and mRNAs are involved in critical signaling pathways in OA cartilage, suggesting their potential as biomarkers or therapeutic targets for OA treatment. Further functional studies are needed to fully elucidate their roles in OA pathogenesis.
本研究旨在鉴定人类骨关节炎（OA）中受损软骨（DC）和未受损软骨（UDC）中差异表达的长链非编码RNA（lncRNA）和信使RNA（mRNA），通过生物信息学分析和ceRNA网络构建探索它们在疾病进展中的作用。分析了5例接受全膝关节置换术的OA患者的软骨样本。采用RNA测序检测DC和UDC样本中lncRNA和mRNA的表达。进行基因本体论（GO）和京都基因与基因组百科全书（KEGG）通路富集分析以研究生物学过程。构建ceRNA网络，并通过定量实时聚合酶链反应（qRT-PCR）验证差异表达的RNA。在受损软骨（DC）样本中，5种lncRNA显著上调，15种显著下调，而8种mRNA上调，8种下调。使用qRT-PCR证实了包括LINC01411、AL596087.2、PCDH20、LRFN2和AL583785.1在内的lncRNA的差异表达，所有结果的p值均显示出统计学意义（p < 0.05）。GO/KEGG富集分析揭示了Ras、PI3K-Akt和MAPK等关键通路，这些通路显著参与OA发病机制。ceRNA网络构建突出了关键的miRNA相互作用，确定了软骨相关生物学过程的潜在调节因子。差异表达的lncRNA和mRNA参与OA软骨的关键信号通路，表明它们作为OA治疗生物标志物或治疗靶点的潜力。需要进一步的功能研究来充分阐明它们在OA发病机制中的作用。
