Zhu KunPeng, Wang XingKai, Fan Lin, Sun Jiao, Chen DePing, He Xiaojian, Zhang ChunLin, Hu ChuanZhen
Department of Orthopedics, Shanghai Tenth People's Hospital, Tongji University, School of Medicine, Shanghai 200072, PR China.
Institute of Bone Tumor, Tongji University, School of Medicine, Shanghai 200072, PR China.
J Cancer. 2025 Aug 11;16(12):3783-3796. doi: 10.7150/jca.118620. eCollection 2025.
Due to the poor prognosis and lack of effective therapy options, treating metastatic osteosarcoma (OS), particularly lung metastasis, presents significant therapeutic challenges. It has been shown that both non-coding RNAs (ncRNAs) and protein-coding mRNAs serve as essential for controlling the progression of tumors. Uncertainty persists regarding the whole expression profile and the network of regulation involving competing endogenous RNAs (ceRNAs) between mRNAs and ncRNAs in the OS lung metastasis. To fully understand variations in the expression of lncRNAs, circRNAs, miRNAs, and mRNAs, we introduced whole transcriptome sequencing (RNA-seq) in the three matched primary and lung-metastasis OS tissues used in the current study. Analysis of Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways and gene ontology (GO) was carried out for mRNAs exhibiting notably distinct expression patterns. After that, the official RNA hybrid and TargetScan databases were utilized to anticipate and establish the ceRNA networks, which are made up of lncRNAs, circRNAs, miRNAs, and mRNAs. Furthermore, two created ceRNA regulatory pathways, lncRNA PCAT1/miR-370-3p/LRAT, and circ_0012586/miR-200b-5p/MFAP5, were chosen at random and verified using a variety of cell and molecular biology experiments. Ultimately, our research may reveal novel avenues for the prevention or treatment of OS lung metastasis as well as fresh evidence for the underlying mechanism.
由于预后较差且缺乏有效的治疗选择，治疗转移性骨肉瘤（OS），尤其是肺转移，面临着重大的治疗挑战。研究表明，非编码RNA（ncRNAs）和蛋白质编码mRNA对于控制肿瘤进展都至关重要。关于骨肉瘤肺转移中mRNA和ncRNAs之间涉及竞争性内源RNA（ceRNAs）的整体表达谱和调控网络仍存在不确定性。为了全面了解长链非编码RNA（lncRNAs）、环状RNA（circRNAs）、微小RNA（miRNAs）和mRNA的表达变化，我们在本研究中使用的三个匹配的原发性和肺转移骨肉瘤组织中引入了全转录组测序（RNA-seq）。对表现出明显不同表达模式的mRNA进行京都基因与基因组百科全书（KEGG）通路和基因本体（GO）分析。之后，利用官方的RNA杂交和TargetScan数据库预测并建立由lncRNAs、circRNAs、miRNAs和mRNA组成的ceRNA网络。此外，随机选择了两个构建的ceRNA调控通路，lncRNA PCAT1/miR-370-3p/LRAT和circ_0012586/miR-200b-5p/MFAP5，并通过各种细胞和分子生物学实验进行验证。最终，我们的研究可能揭示预防或治疗骨肉瘤肺转移的新途径以及潜在机制的新证据。
