Orthopaedic Department, The Second Xiangya Hospital of Central South Unniversity, Hunan Province, Changsha, China.
Orthopaedic Department, The Third Xiangya Hospital of Central South University, Hunan Province, Changsha, China.
Funct Integr Genomics. 2024 Nov 22;24(6):219. doi: 10.1007/s10142-024-01504-x.
The objective of this research is to investigate the function of long non-coding RNA (lncRNA) associated with disulfidptosis, particularly LINC01137, in osteosarcoma (OS), and its impact on macrophage polarization and the tumor immune microenvironment (TME), with the goal of identifying new prognostic biomarkers and therapeutic targets. Utilizing the OS transcriptome dataset from the TARGET database, differentially expressed lncRNAs related to disulfidptosis were identified. The functional mechanisms of LINC01137, which affect cell proliferation, migration, invasiveness, programmed cell death, and macrophage orientation, were explored using the full suite of analyses provided by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), alongside a diverse array of laboratory experiments, including an in vivo osteosarcoma xenograft model in BALB/c nude mice to assess the impact of LINC01137 knockdown on tumor growth. Among three lncRNAs identified that were distinctly linked to disulfidptosis, LINC01137 showed a notable increase in expression within OS cell lines. Silencing LINC01137 led to a marked decrease in the abilities of cell proliferation, migration, and invasiveness, simultaneously enhancing programmed cell death and facilitating the process of epithelial-mesenchymal transition (EMT). In vivo experiments further confirmed that LINC01137 knockdown significantly suppressed tumor growth in osteosarcoma xenograft models, aligning with the in vitro findings. Associated with disulfidptosis, LINC01137 is pivotal in osteosarcoma development through its enhancement of tumor cell proliferation, migration, and invasiveness, as well as its modification of macrophage orientation within the TME. Given its significance, LINC01137 merits exploration as a prognostic indicator, necessitating detailed studies on its regulatory functions and potential in therapy.
本研究旨在探讨与二硫键细胞死亡相关的长链非编码 RNA(lncRNA)的功能,特别是 LINC01137,在骨肉瘤(OS)中的作用,及其对巨噬细胞极化和肿瘤免疫微环境(TME)的影响,以期鉴定新的预后生物标志物和治疗靶点。利用 TARGET 数据库中的 OS 转录组数据集,鉴定出与二硫键细胞死亡相关的差异表达 lncRNA。通过 Gene Ontology(GO)和 Kyoto Encyclopedia of Genes and Genomes(KEGG)提供的全套分析,以及一系列实验室实验,包括在 BALB/c 裸鼠体内骨肉瘤异种移植模型中评估 LINC01137 敲低对肿瘤生长的影响,探讨了 LINC01137 影响细胞增殖、迁移、侵袭、程序性细胞死亡和巨噬细胞定向的功能机制。在与二硫键细胞死亡明显相关的三种 lncRNA 中,LINC01137 在 OS 细胞系中表达明显增加。沉默 LINC01137 导致细胞增殖、迁移和侵袭能力显著下降,同时增强程序性细胞死亡并促进上皮-间充质转化(EMT)过程。体内实验进一步证实,LINC01137 敲低显著抑制骨肉瘤异种移植模型中的肿瘤生长,与体外实验结果一致。与二硫键细胞死亡相关,LINC01137 通过增强肿瘤细胞增殖、迁移和侵袭能力,以及改变 TME 中巨噬细胞定向,在骨肉瘤发生发展中起关键作用。鉴于其重要性,LINC01137 值得作为预后指标进行探索,需要对其调控功能及其在治疗中的潜力进行详细研究。