Objective:This study aimed to elucidate the regulatory mechanisms of the long intergenic non-protein codingRNA 02381(LINC02381)/microRNA-let-7g-5p(let-7g-5p)/thrombospondin 1(THBS1) signaling axis in osteosarcoma (OS).Methods:The expression levels ofLINC02381,let-7g-5p, andTHBS1were quantified in OS and adjacent normal tissues via reverse transcription quantitative polymerase chain reaction. Their correlations with clinicopathological features were analyzed. Expression patterns were further validated in OS cell lines (143B, U-2OS, Saos-2, MNNG-HOS, MG-63) and normal osteoblast cell line hFOB1.19. The molecular interaction betweenLINC02381andlet-7g-5pand the targeting relationship oflet-7g-5pwithTHBS1were verified via dual-luciferase reporter and RNA pull-down assays. Functional effects were assessed using cell counting kit-8, colony formation, Transwell migration, and xenograft tumor models.Results:Compared to adjacent normal tissues,LINC02381andTHBS1were upregulated in OS tissues (fold change > 3.0,p< 0.001), whilelet-7g-5pwas downregulated (fold change ≈ 0.038,p< 0.001). Similar expression trends were observed in U-2OS cells. Knockdown ofLINC02381or overexpression oflet-7g-5preduced cell proliferation, colony formation, migration,THBS1expression, and tumor volume (p< 0.001). These inhibitory effects were partially reversed bylet-7g-5pinhibitors, restoring cell viability and migration by approximately 70%. Mechanistically,LINC02381functioned as a competing endogenous RNA (ceRNA), directly binding tolet-7g-5pand mitigating its suppression ofTHBS1.Conclusions:LINC02381promotes OA progression by acting as a ceRNA forlet-7g-5p, thereby upregulatingTHBS1expression. This signaling axis represents a potential therapeutic target for OS.
目的：本研究旨在阐明长链基因间非编码RNA 02381（LINC02381）/微小RNA-let-7g-5p（let-7g-5p）/血小板反应蛋白1（THBS1）信号轴在骨肉瘤（OS）中的调控机制。方法：通过逆转录定量聚合酶链反应检测LINC02381、let-7g-5p和THBS1在骨肉瘤组织及癌旁正常组织中的表达水平，并分析其与临床病理特征的相关性。在骨肉瘤细胞系（143B、U-2OS、Saos-2、MNNG-HOS、MG-63）及正常成骨细胞系hFOB1.19中进一步验证表达模式。通过双荧光素酶报告基因实验和RNA pull-down实验验证LINC02381与let-7g-5p之间的分子相互作用以及let-7g-5p对THBS1的靶向关系。使用细胞计数试剂盒-8、克隆形成、Transwell迁移及异种移植瘤模型评估功能效应。结果：与癌旁正常组织相比，LINC02381和THBS1在骨肉瘤组织中表达上调（倍数变化>3.0，p<0.001），而let-7g-5p表达下调（倍数变化≈0.038，p<0.001）。在U-2OS细胞中观察到相似表达趋势。敲低LINC02381或过表达let-7g-5p可抑制细胞增殖、克隆形成、迁移、THBS1表达及肿瘤体积（p<0.001）。这些抑制效应可被let-7g-5p抑制剂部分逆转，使细胞活力和迁移能力恢复约70%。机制上，LINC02381作为竞争性内源RNA（ceRNA），直接结合let-7g-5p并减轻其对THBS1的抑制作用。结论：LINC02381通过作为let-7g-5p的ceRNA上调THBS1表达，从而促进骨肉瘤进展。该信号轴是骨肉瘤的潜在治疗靶点。
TheLINC02381/let-7g-5p/THBS1Signaling Axis Modulates Cellular Proliferative Activity in Osteosarcoma
肿瘤(癌症)患者之家