研究动态
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原标题:Primary and Secondary micro-RNA 调节肝细胞癌的外在凋亡通路。

[Primary and Secondary micro-RNA Modulation the Extrinsic Pathway of Apoptosis in Hepatocellular Carcinoma].

发表日期:2023
作者: T M Khlebodarova, P S Demenkov, T V Ivanisenko, E A Antropova, I N Lavrik, V A Ivanisenko
来源: Cell Death & Disease

摘要:

肝细胞肝癌是最常见的恶性肝脏疾病之一,具有高复发率和低五年存活率。其结构及不同患者之间存在很大差异,这增加了诊断、预后和治疗的复杂性。因此,个体化的患者中心方法变得非常重要,在这种方法中,使用与该疾病发病机制有关的模因物和hsa-miRNA抑制剂可能是至关重要的。从这个角度来看,hsa-miRNA非常有趣,它们的异常表达与病人的预后不良有关,并且由于程序性细胞死亡(凋亡)的失调而与肿瘤进展相关。然而,hsa-miRNA对肿瘤发展的影响不仅取决于它对基因表达的直接影响,即主要靶点,而且还取决于由调节途径介导的次要靶点。虽然前者正在积极研究,但这些hsa-miRNA次要靶点在调节凋亡方面的作用仍不清楚。本研究总结了hsa-miRNAs的数据,其主要靶点是凋亡外在途径的关键基因。它们的异常表达与早期疾病复发和病人预后不良有关。对于这些hsa-miRNAs,我们使用ANDSystem软件包重建了对次要靶点表达的调节,并分析了它们对凋亡外在途径活性的影响。hsa-miRNAs通过对次要靶点的作用可能产生的效应与其对主要靶点数量呈负相关。同时,研究结果表明,hsa-miR-373、hsa-miR-106b和hsa-miR-96具有最高的肝细胞肝癌标记物优先级,它们对次要靶点的作用增强了它们的抗凋亡作用。
One of the most common malignant liver diseases is hepatocellular carcinoma, which has a high recurrence rate and a low five-year survival rate. It is very heterogeneous both in structure and between patients, which complicates the diagnosis, prognosis and response to treatment. In this regard, an individualized, patient-centered approach becomes important, in which the use of mimetics and hsa-miRNA inhibitors involved in the pathogenesis of the disease may be determinative. From this point of view hsa-miRNAs are of interest, their aberrant expression is associated with poor prognosis for patients and is associated with tumor progression due to dysregulation of programmed cell death (apoptosis). However, the effect of hsa-miRNA on tumor development depends not only on its direct effect on expression of genes, the primary targets, but also on secondary targets mediated by regulatory pathways. While the former are actively studied, the role of secondary targets of these hsa-miRNAs in modulating apoptosis is still unclear. The present work summarizes data on hsa-miRNAs whose primary targets are key genes of the extrinsic pathway of apoptosis. Their aberrant expression is associated with early disease relapse and poor patient outcome. For these hsa-miRNAs, using the software package ANDSystem, we reconstructed the regulation of the expression of secondary targets and analyzed their impact on the activity of the extrinsic pathway of apoptosis. The potential effect of hsa-miRNAs mediated by action on secondary targets is shown to negatively correlate with the number of primary targets. It is also shown that hsa-miR-373, hsa-miR-106b and hsa-miR-96 have the highest priority as markers of hepatocellular carcinoma, whose action on secondary targets enhances their anti-apoptotic effect.