Thanyaphoo Suphannee, Sae-Lee Chanachai, Thaopech Wilasinee, Amornrit Warisa, Junking Mutita, Yenchitsomanus Pa-Thai, Poungvarin Naravat
Clinical Molecular Pathology Laboratory, Department of Clinical Pathology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
Research Division, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
PLoS One. 2025 May 6;20(5):e0322307. doi: 10.1371/journal.pone.0322307. eCollection 2025.
Newcastle Disease Virus (NDV) has emerged as a promising oncolytic viral therapy for various human cancers; however, its effectiveness against cholangiocarcinoma (CCA) remains unexplored. This study presents the capability of the lentogenic LaSota strain of NDV to eliminate two CCA cell lines, KKU-055 and KKU-100, as well as the potential molecular mechanisms underlying this effect. Comprehensive transcriptome analysis revealed alterations in gene expression within several pathways in CCA cells following exposure to the LaSota strain NDV, including those involved in TNF-alpha signaling via NF-kB, interferon alpha response, apoptosis, and IL-6/JAK/STAT3 signaling pathways. We remarkably observed a contrasting alteration in the expression of CXCR4, GRAMD1B, IGFBP4, and TGM2 genes in KKU-055 and KKU-100 cells. In addition, gene network analysis highlighted CCNA2, CDK1, DDX58, DHX58, EXO1, GBP1, IFIH1, IFIT1, IFIT2, IFIT3, IRF7, ISIG15, MX1, OAS1, OAS2, PARP9, TOP2A and XAF1 as potential hub genes influencing the response of CCA cells to NDV LaSota strain. Our findings offer evidence supporting the promise of NDV-based therapies as potential strategies for eliminating CCA cells.
新城疫病毒（NDV）已成为一种有前景的用于治疗多种人类癌症的溶瘤病毒疗法；然而，其对胆管癌（CCA）的有效性仍未得到探索。本研究展示了新城疫病毒弱毒株LaSota消除两种CCA细胞系KKU - 055和KKU - 100的能力，以及这种效应背后潜在的分子机制。全面的转录组分析揭示了暴露于LaSota株新城疫病毒后CCA细胞中多个通路的基因表达变化，包括那些通过NF - kB参与肿瘤坏死因子 - α信号传导、干扰素α反应、细胞凋亡以及白细胞介素 - 6/Janus激酶/信号转导和转录激活因子3信号通路的基因。我们显著观察到KKU - 055和KKU - 100细胞中CXCR4、GRAMD1B、胰岛素样生长因子结合蛋白4（IGFBP4）和转谷氨酰胺酶2（TGM2）基因表达的相反变化。此外，基因网络分析突出了细胞周期蛋白A2（CCNA2）、细胞周期蛋白依赖性激酶1（CDK1）、解旋酶DDX58、解旋酶DHX58、核酸外切酶1（EXO1）、鸟苷结合蛋白1（GBP1）、干扰素诱导解旋酶C结构域蛋白1（IFIH1）、干扰素诱导蛋白15（IFIT1）、干扰素诱导蛋白35（IFIT2）、干扰素诱导蛋白6（IFIT3）、干扰素调节因子7（IRF7）、干扰素刺激基因15（ISG15）、Mx蛋白1（MX1）、2'-5'-寡腺苷酸合成酶1（OAS1）、2'-5'-寡腺苷酸合成酶2（OAS2）、聚（ADP - 核糖）聚合酶9（PARP9）、拓扑异构酶2α（TOP2A）和凋亡抑制蛋白X相关因子1（XAF1）作为影响CCA细胞对新城疫病毒LaSota株反应的潜在枢纽基因。我们的研究结果为基于新城疫病毒的疗法作为消除CCA细胞的潜在策略的前景提供了证据支持。
