Department of General Surgery, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330006, Jiangxi, China.
Department of Clinical Microbiology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330006, Jiangxi, China.
Funct Integr Genomics. 2024 Mar 5;24(2):49. doi: 10.1007/s10142-024-01329-8.
Long noncoding RNAs (lncRNAs) play important roles in modulating the tumorigenesis and progression of malignant tumors. LINC02086 is a newly identified oncogene associated with tumorigenesis, but its role in pancreatic cancer (PC) has not been fully elucidated. In this study we examined the expression levels of LINC02086, miR-342-3p, and CA9 in PC. The relationship of ferroptosis with these factors was analyzed by detecting the expression levels of Fe, reactive oxygen species (ROS), and ferroptosis marker proteins. The expression of these genes was altered to observe their effects on cell proliferation, migration, and invasion ability. Bioinformatics was used to predict target genes, and the binding relationship was verified luciferase reporter assay. Finally, the function of LINC02086 was evaluated in vivo. The findings suggest that LINC02086 is highly expressed in PC tissues and cell lines and is correlated with a poor prognosis. In vitro experiments demonstrated that LINC02086 knockdown promoted ferroptosis in PC cells to suppress their malignant phenotype. LINC02086 acts as a competitive endogenous RNA that adsorbed miR-342-3p. miR-342-3p hinders the malignant progression of PC by promoting ferroptosis. In addition, miR-342-3p targets CA9 and affects its function. Further mechanistic studies revealed that LINC02086 inhibits ferroptosis and promotes PC progression by acting as a sponge for miR-342-3p to upregulate CA9 expression. In vivo experiments further confirmed this mechanism. Taken together, LINC02086 upregulates CA9 expression by competitively binding with miR-342-3p, thereby inhibiting ferroptosis in PC cells and promoting their malignant phenotype. The results of our study provide new insights into how LINC02086 contributes to the progression of PC.
长链非编码 RNA（lncRNA）在调节恶性肿瘤的发生和发展中发挥重要作用。LINC02086 是一种新鉴定的与肿瘤发生相关的癌基因，但它在胰腺癌（PC）中的作用尚未完全阐明。在本研究中，我们检测了 PC 中 LINC02086、miR-342-3p 和 CA9 的表达水平。通过检测铁、活性氧（ROS）和铁死亡标记蛋白的表达水平，分析了这些因素与铁死亡的关系。改变这些基因的表达水平，观察它们对细胞增殖、迁移和侵袭能力的影响。利用生物信息学预测靶基因，并通过荧光素酶报告基因实验验证结合关系。最后，在体内评估 LINC02086 的功能。研究结果表明，LINC02086 在 PC 组织和细胞系中高表达，与预后不良相关。体外实验表明，LINC02086 敲低可促进 PC 细胞发生铁死亡，抑制其恶性表型。LINC02086 作为竞争性内源性 RNA 吸附 miR-342-3p。miR-342-3p 通过促进铁死亡抑制 PC 的恶性进展。此外，miR-342-3p 靶向 CA9 并影响其功能。进一步的机制研究表明，LINC02086 通过作为 miR-342-3p 的海绵来上调 CA9 表达，抑制铁死亡并促进 PC 进展。体内实验进一步证实了这一机制。综上所述，LINC02086 通过与 miR-342-3p 竞争性结合来上调 CA9 表达，从而抑制 PC 细胞中的铁死亡并促进其恶性表型。我们的研究结果为 LINC02086 促进 PC 进展的机制提供了新的见解。
