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Updated: May 12, 2025
Genome-wide RNAi Screening to Identify Host Factors That Modulate Oncolytic Virus Therapy
Published on: April 3, 2018
Transcriptome insights into newcastle disease virus-mediated eradication of cholangiocarcinoma cells
Suphannee Thanyaphoo1,2, Chanachai Sae-Lee1,2, Wilasinee Thaopech3
1Clinical Molecular Pathology Laboratory, Department of Clinical Pathology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
Abstract:
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.
Insights
Newcastle Disease Virus (NDV) shows potential for eliminating cholangiocarcinoma (CCA) cells. This study explored NDV
Area of Science:
- Oncology
- Virology
- Molecular Biology
Background:
- Newcastle Disease Virus (NDV) is a promising oncolytic virus for cancer therapy.
- Its efficacy against cholangiocarcinoma (CCA) is currently unknown.
Purpose of the Study:
- To investigate the potential of the lentogenic LaSota strain of NDV in eliminating CCA cells.
- To elucidate the molecular mechanisms underlying NDV's effect on CCA.
Main Methods:
- Exposure of two CCA cell lines (KKU-055 and KKU-100) to NDV LaSota strain.
- Comprehensive transcriptome analysis to identify altered gene expression pathways.
- Gene network analysis to pinpoint potential hub genes.
Main Results:
- NDV LaSota strain demonstrated the ability to eliminate KKU-055 and KKU-100 CCA cell lines.
- Transcriptome analysis revealed significant alterations in TNF-alpha, interferon alpha, apoptosis, and IL-6/JAK/STAT3 signaling pathways.
- Contrasting gene expression changes in CXCR4, GRAMD1B, IGFBP4, and TGM2 were observed; several potential hub genes were identified.
Conclusions:
- NDV LaSota strain exhibits oncolytic potential against cholangiocarcinoma.
- The study identified key molecular pathways and genes involved in the response of CCA cells to NDV, supporting its development as a therapeutic strategy.
