Department of Thyroid and Breast Surgery, The Second Affiliated Hospital of Soochow University, Suzhou, China.
Department of Oncology, The Second Affiliated Hospital of Soochow University, Suzhou, China.
J Cell Mol Med. 2024 Nov;28(22):e70227. doi: 10.1111/jcmm.70227.
The aim of this study was to investigate whether long intergenic non-coding RNA 1929 (LINC01929), a novel long non-coding RNA, could serve as a prognostic biomarker for various tumours and explore its function. The expression and prognosis of LINC01929 across 33 different tumour types in patients in the Cancer Genome Atlas (TCGA) database were analysed. Also, the correlation between LINC01929 expression, tumour mutational burden (TMB), microsatellite instability (MSI), immune checkpoint status and immune cell infiltration was examined. Moreover, the function of LINC01929 in the breast cancer cell lines was explored via CCK-8, colony formation and cell cycle assays. In addition, the downstream mechanisms of LINC01929 were analysed via transcriptome sequencing, RT-qPCR, and western blotting. Our analysis revealed that LINC01929 was weakly expressed in 3 tumour types and highly expressed in 14 tumour types, and low expression of LINC01929 was correlated with better clinical outcomes in 15 tumour types. Furthermore, LINC01929 expression was correlated significantly with the TMB, MSI, immune checkpoint and immune cell infiltration across multiple tumour types. The knockdown of LINC01929 inhibited cell cycle progression, cell proliferation, and tumorigenesis and downregulated the TNF pathway and STAT3 expression. The treatment with exogenous TNF-α partially reversed the cell cycle progression and proliferation inhibition caused by LINC01929 knockdown, and these effects were accompanied by changes in STAT3 expression. LINC01929 may serve as an effective biomarker affecting the TMB, MSI, immune cell infiltration and immune checkpoint status. Mechanistically, LINC01929 affects cell cycle progression and cell proliferation through the TNF/STAT3 axis. These findings offer valuable insights into the potential applications of LINC01929 in tumour therapy, which may yield novel targets and strategies for the diagnosis and treatment of patients.
本研究旨在探讨长链非编码 RNA 1929(LINC01929)是否可以作为各种肿瘤的预后生物标志物,并探索其功能。分析了癌症基因组图谱(TCGA)数据库中 33 种不同肿瘤类型患者中 LINC01929 的表达和预后。还检查了 LINC01929 表达与肿瘤突变负担(TMB)、微卫星不稳定性(MSI)、免疫检查点状态和免疫细胞浸润之间的相关性。此外,通过 CCK-8、集落形成和细胞周期测定法研究了 LINC01929 在乳腺癌细胞系中的功能。此外,通过转录组测序、RT-qPCR 和 Western blot 分析了 LINC01929 的下游机制。我们的分析表明,LINC01929 在 3 种肿瘤类型中表达较弱,在 14 种肿瘤类型中表达较高,在 15 种肿瘤类型中低表达 LINC01929 与更好的临床结果相关。此外,LINC01929 的表达与多种肿瘤类型的 TMB、MSI、免疫检查点和免疫细胞浸润显著相关。LINC01929 的敲低抑制细胞周期进程、细胞增殖和肿瘤发生,并下调 TNF 途径和 STAT3 表达。外源性 TNF-α 的处理部分逆转了 LINC01929 敲低引起的细胞周期进程和增殖抑制,这些作用伴随着 STAT3 表达的变化。LINC01929 可能作为影响 TMB、MSI、免疫细胞浸润和免疫检查点状态的有效生物标志物。从机制上讲,LINC01929 通过 TNF/STAT3 轴影响细胞周期进程和细胞增殖。这些发现为 LINC01929 在肿瘤治疗中的潜在应用提供了有价值的见解,这可能为患者的诊断和治疗提供新的靶点和策略。