PDF(Pubmed)
Abstract：
BACKGROUND: 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.
METHODS: 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 in vitro 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.
RESULTS: 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.
CONCLUSIONS: 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.
METHODS: 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 in vitro 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.
RESULTS: 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.
CONCLUSIONS: 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.
摘要：
背景：胆管癌（CCA）是世界上最致命的癌症之一。它通常预后不良，并且在早期阶段难以识别。长非编码RNA（lncRNAs）在越来越多的研究中被证明在信号通路的控制中是重要的。细胞行为，和表观遗传修饰有助于肿瘤的生长。这项工作的目的是检查CCA和lncRNAAL161431.1之间的关系。
方法：使用TCGA临床生存数据，我们评估了AL161431.1表达与患者预后之间的相关性.使用程序集群ProfilerR，进行富集分析。此外,免疫细胞浸润和AL161431.1表达之间的关联通过TCGA数据库的综述进行了评估.接下来,为了确定AL161431.1是否影响肿瘤生长，迁移,和入侵CCA，进行了体外功能测定。采用定量实时聚合酶链反应(qPCR)来测量CCA细胞中的AL161431.1表达水平。蛋白质印迹用于测量蛋白质水平。
结果：在CCA中，AL161431.1表达异常。高风险组患者的总体生存率（OS）明显低于低风险组患者。对TCGA数据的更彻底的观察表明，AL161431.1的高表达水平与T细胞浸润增加之间存在关系，T辅助细胞,和NKCD56dim细胞。此外，在CCA细胞中AL161431.1敲低阻碍了侵袭，迁移,并降低磷酸化Smad2/Smad3的表达以抑制TGFβ/SMAD信号通路。
结论：我们的结果表明lncRNAAL161431.1激活TGFβ/SMAD信号通路以增强CCA发育和转移。AL161431.1可能是胆管癌治疗的新靶标或诊断标志物。
方法：使用TCGA临床生存数据，我们评估了AL161431.1表达与患者预后之间的相关性.使用程序集群ProfilerR，进行富集分析。此外,免疫细胞浸润和AL161431.1表达之间的关联通过TCGA数据库的综述进行了评估.接下来,为了确定AL161431.1是否影响肿瘤生长，迁移,和入侵CCA，进行了体外功能测定。采用定量实时聚合酶链反应(qPCR)来测量CCA细胞中的AL161431.1表达水平。蛋白质印迹用于测量蛋白质水平。
结果：在CCA中，AL161431.1表达异常。高风险组患者的总体生存率（OS）明显低于低风险组患者。对TCGA数据的更彻底的观察表明，AL161431.1的高表达水平与T细胞浸润增加之间存在关系，T辅助细胞,和NKCD56dim细胞。此外，在CCA细胞中AL161431.1敲低阻碍了侵袭，迁移,并降低磷酸化Smad2/Smad3的表达以抑制TGFβ/SMAD信号通路。
结论：我们的结果表明lncRNAAL161431.1激活TGFβ/SMAD信号通路以增强CCA发育和转移。AL161431.1可能是胆管癌治疗的新靶标或诊断标志物。
