The Third Affiliated Hospital of Nanchang University, North 128 Xiangshan Road, Nanchang, Jiangxi, 330008, P.R. China.
Department of Orthopedics, The First Hospital of Nanchang, North 128 Xiangshan Road, Nanchang, Jiangxi, 330008, P.R. China.
BMC Cancer. 2024 Feb 2;24(1):166. doi: 10.1186/s12885-024-11901-x.
Osteosarcoma (OS) is a highly malignant tumor, and its dysregulated lipid metabolism is associated with tumorigenesis and unfavorable prognosis. Interestingly, long noncoding RNAs (lncRNAs) have emerged as pivotal regulators of lipid metabolism, exerting notable impacts on tumor proliferation. Nevertheless, the involvement of RPARP-AS1, a novel lipid metabolism-associated lncRNA, remains unexplored in the context of OS. This study aims to identify functionally relevant lncRNAs impacting OS proliferation and lipid metabolism and seeks to shed light on the upstream regulatory mechanisms governing lipogenic enzyme activity. Based on comprehensive bioinformatic analysis and the establishment of a risk model, we identified seven lncRNAs significantly associated with clinical characteristics and lipid metabolism-related genes in patients with OS. Among these, RPARP-AS1 was selected for in-depth investigation regarding its roles in OS proliferation and lipid metabolism. Experimental techniques including RT-qPCR, Western blot, cell viability assay, assessment, and quantification of free fatty acids (FFAs) and triglycerides (TGs) were utilized to elucidate the functional significance of RPARP-AS1 in OS cells and validate its effects on lipid metabolism. Manipulation of RPARP-AS1 expression via ectopic expression or siRNA-mediated knockdown led to alterations in epithelial-mesenchymal transition (EMT) and expression of apoptosis-associated proteins, thereby influencing OS cell proliferation and apoptosis. Mechanistically, RPARP-AS1 was found to augment the expression of key lipogenic enzymes (FABP4, MAGL, and SCD1) and potentially modulate the Akt/mTOR pathway, thereby contributing to lipid metabolism (involving alterations in FFA and TG levels) in OS cells. Collectively, our findings establish RPARP-AS1 as a novel oncogene in OS cells and suggest its role in fostering tumor growth through the enhancement of lipid metabolism.
骨肉瘤（OS）是一种高度恶性的肿瘤，其失调的脂质代谢与肿瘤发生和不良预后有关。有趣的是，长链非编码 RNA（lncRNA）已成为脂质代谢的关键调节因子，对肿瘤增殖有显著影响。然而，RPARP-AS1 作为一种新的与脂质代谢相关的 lncRNA，其在 OS 中的作用仍未被探索。本研究旨在鉴定影响 OS 增殖和脂质代谢的功能相关 lncRNA，并探讨调控脂肪生成酶活性的上游调节机制。通过全面的生物信息学分析和风险模型的建立，我们鉴定出了 7 个与 OS 患者临床特征和脂质代谢相关基因显著相关的 lncRNA。其中，RPARP-AS1 被选中进行深入研究，以探讨其在 OS 增殖和脂质代谢中的作用。我们利用 RT-qPCR、Western blot、细胞活力测定、游离脂肪酸（FFAs）和甘油三酯（TGs）的评估和定量等实验技术，阐明了 RPARP-AS1 在 OS 细胞中的功能意义，并验证了其对脂质代谢的影响。通过过表达或 siRNA 介导的敲低来操纵 RPARP-AS1 的表达，导致上皮-间充质转化（EMT）和凋亡相关蛋白的表达发生变化，从而影响 OS 细胞的增殖和凋亡。机制上，发现 RPARP-AS1 上调了关键的脂肪生成酶（FABP4、MAGL 和 SCD1）的表达，并可能调节 Akt/mTOR 通路，从而促进 OS 细胞的脂质代谢（涉及 FFA 和 TG 水平的变化）。综上所述，我们的研究结果确立了 RPARP-AS1 作为 OS 细胞中的一种新的癌基因，并表明其通过增强脂质代谢促进肿瘤生长的作用。
