Department of Radiation Oncology, General Hospital of Ningxia Medical University; Cancer Institute, Ningxia Medical University, Yinchuan 750004, Ningxia, PR China.
Department of Cardiology, Ningxia Medical University, Yinchuan 750004, Ningxia, PR China.
Aging (Albany NY). 2024 Aug 1;16(15):11501-11512. doi: 10.18632/aging.205898.
Cholangiocarcinoma (CCA) is one of the most deadly cancers in the world. It usually has a bad prognosis and is challenging to identify in its early stages. Long noncoding RNAs (lncRNAs) have been shown in an increasing number of studies to be important in the control of signaling pathways, cell behaviors, and epigenetic modification that contribute to the growth of tumors. The purpose of this work was to examine the relationship between CCA and lncRNA AL161431.1.
Using TCGA clinical survival data, we evaluated the association between AL161431.1 expression and patient prognosis. Using the program cluster Profiler R, enrichment analysis was performed. Additionally, the association between immune cell infiltration and AL161431.1 expression was evaluated by a review of the TCGA database. Next, to ascertain if AL161431.1 influences tumor growth, migration, and invasion in CCA, functional assays were conducted. Quantitative real-time polymerase chain reaction (qPCR) was employed to gauge AL161431.1 expression levels in CCA cells. Western blot was used to measure protein levels.
In CCA, AL161431.1 was extremely expressed. The patients in the high-risk group had a significantly poorer overall survival (OS) than the patients in the low-risk group. A more thorough look at the TCGA data showed a relationship between high expression levels of AL161431.1 and increased infiltration of T cells, T helper cells, and NK CD56dim cells. Furthermore, AL161431.1 knockdown in CCA cells impeded invasion, migration, and proliferation and also lowered the expression of phosphorylated Smad2/Smad3 to restrain the TGFβ/SMAD signaling pathway.
Our results indicate that the lncRNA AL161431.1 activates the TGFβ/SMAD signaling pathway to enhance CCA development and metastasis. AL161431.1 could be a novel target for cholangiocarcinoma treatment or a diagnostic marker.
胆管癌（CCA）是世界上最致命的癌症之一。它通常预后不良，在早期阶段难以识别。越来越多的研究表明，长链非编码 RNA（lncRNA）在控制信号通路、细胞行为和表观遗传修饰方面发挥着重要作用，这些修饰有助于肿瘤的生长。本研究旨在探讨 CCA 与 lncRNA AL161431.1 的关系。
使用 TCGA 临床生存数据，我们评估了 AL161431.1 表达与患者预后的关系。使用程序 cluster Profiler R 进行富集分析。此外，通过查阅 TCGA 数据库评估了免疫细胞浸润与 AL161431.1 表达的关系。接下来，为了确定 AL161431.1 是否影响 CCA 中的肿瘤生长、迁移和侵袭，进行了功能测定。采用实时定量聚合酶链反应（qPCR）检测 CCA 细胞中 AL161431.1 的表达水平。采用 Western blot 检测蛋白水平。
在 CCA 中，AL161431.1 呈高表达。高风险组患者的总生存期（OS）明显低于低风险组患者。更深入地研究 TCGA 数据显示，AL161431.1 高表达与 T 细胞、T 辅助细胞和 NK CD56dim 细胞浸润增加有关。此外，在 CCA 细胞中敲低 AL161431.1 可抑制侵袭、迁移和增殖，并降低磷酸化 Smad2/Smad3 的表达，从而抑制 TGFβ/SMAD 信号通路。
我们的研究结果表明，lncRNA AL161431.1 通过激活 TGFβ/SMAD 信号通路促进 CCA 的发展和转移。AL161431.1 可能成为胆管癌治疗的新靶点或诊断标志物。
