# Transcriptome insights into newcastle disease virus-mediated eradication of cholangiocarcinoma cells

**Authors:** Suphannee Thanyaphoo, Chanachai Sae-Lee, Wilasinee Thaopech, Warisa Amornrit, Mutita Junking, Pa-thai Yenchitsomanus, Naravat Poungvarin

PMC · DOI: 10.1371/journal.pone.0322307 · PLOS One · 2025-05-06

## TL;DR

This study explores how a strain of Newcastle Disease Virus can kill cholangiocarcinoma cells and identifies key genes and pathways involved in this process.

## Contribution

The study is the first to investigate the effectiveness of NDV against cholangiocarcinoma and identifies novel gene expression patterns and hub genes.

## Key findings

- The LaSota strain of NDV effectively eliminates two cholangiocarcinoma cell lines.
- Transcriptome analysis reveals altered gene expression in pathways like TNF-alpha signaling and apoptosis.
- Key hub genes such as CCNA2, CDK1, and IFIT1 are identified as influencing the response to NDV.

## 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.

## Linked entities

- **Genes:** CXCR4 (C-X-C motif chemokine receptor 4) [NCBI Gene 7852], GRAMD1B (GRAM domain containing 1B) [NCBI Gene 57476], IGFBP4 (insulin like growth factor binding protein 4) [NCBI Gene 3487], TGM2 (transglutaminase 2) [NCBI Gene 7052], CCNA2 (cyclin A2) [NCBI Gene 890], CDK1 (cyclin dependent kinase 1) [NCBI Gene 983], RIGI (RNA sensor RIG-I) [NCBI Gene 23586], DHX58 (DExH-box helicase 58) [NCBI Gene 79132], EXO1 (exonuclease 1) [NCBI Gene 9156], GBP1 (guanylate binding protein 1) [NCBI Gene 2633], IFIH1 (interferon induced with helicase C domain 1) [NCBI Gene 64135], IFIT1 (interferon induced protein with tetratricopeptide repeats 1) [NCBI Gene 3434], IFIT2 (interferon induced protein with tetratricopeptide repeats 2) [NCBI Gene 3433], IFIT3 (interferon induced protein with tetratricopeptide repeats 3) [NCBI Gene 3437], IRF7 (interferon regulatory factor 7) [NCBI Gene 3665], MX1 (MX dynamin like GTPase 1) [NCBI Gene 4599], OAS1 (2'-5'-oligoadenylate synthetase 1) [NCBI Gene 4938], OAS2 (2'-5'-oligoadenylate synthetase 2) [NCBI Gene 4939], PARP9 (poly(ADP-ribose) polymerase family member 9) [NCBI Gene 83666], TOP2A (DNA topoisomerase II alpha) [NCBI Gene 7153], XAF1 (XIAP associated factor 1) [NCBI Gene 54739]
- **Diseases:** cholangiocarcinoma (MONDO:0019087)

## Full-text entities

- **Genes:** GBP1 (guanylate binding protein 1) [NCBI Gene 2633] {aka hGBP1}, CXCR4 (C-X-C motif chemokine receptor 4) [NCBI Gene 7852] {aka CD184, D2S201E, FB22, HM89, HSY3RR, LCR1}, IFIT2 (interferon induced protein with tetratricopeptide repeats 2) [NCBI Gene 3433] {aka G10P2, GARG-39, IFI-54, IFI-54K, IFI54, IFIT-2}, IFIT3 (interferon induced protein with tetratricopeptide repeats 3) [NCBI Gene 3437] {aka CIG-49, GARG-49, IFI60, IFIT4, IRG2, ISG60}, RIGI (RNA sensor RIG-I) [NCBI Gene 23586] {aka DDX58, RIG-I, RIG1, RLR-1, SGMRT2}, CCNA2 (cyclin A2) [NCBI Gene 890] {aka CCN1, CCNA}, GRAMD1B (GRAM domain containing 1B) [NCBI Gene 57476] {aka LAMb, LINC01059}, OAS2 (2'-5'-oligoadenylate synthetase 2) [NCBI Gene 4939] {aka AIAISD2}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, TGM2 (transglutaminase 2) [NCBI Gene 7052] {aka G(h), TG(C), TGC, hTG2, tTG}, IFIH1 (interferon induced with helicase C domain 1) [NCBI Gene 64135] {aka AGS7, Hlcd, IDDM19, IMD95, MDA-5, MDA5}, DHX58 (DExH-box helicase 58) [NCBI Gene 79132] {aka D11LGP2, D11lgp2e, LGP2, RLR-3}, EXO1 (exonuclease 1) [NCBI Gene 9156] {aka HEX1, hExoI}, TOP2A (DNA topoisomerase II alpha) [NCBI Gene 7153] {aka TOP2, TOP2alpha, TOPIIA, TP2A}, CDK1 (cyclin dependent kinase 1) [NCBI Gene 983] {aka CDC2, CDC28A, P34CDC2}, PARP9 (poly(ADP-ribose) polymerase family member 9) [NCBI Gene 83666] {aka ARTD9, BAL, BAL1, MGC:7868}, OAS1 (2'-5'-oligoadenylate synthetase 1) [NCBI Gene 4938] {aka E18/E16, IFI-4, IMD100, OIAS, OIASI}, MX1 (MX dynamin like GTPase 1) [NCBI Gene 4599] {aka IFI-78K, IFI78, MX, MxA, lncMX1-215}, IRF7 (interferon regulatory factor 7) [NCBI Gene 3665] {aka IMD39, IRF-7, IRF-7H, IRF7A, IRF7B, IRF7C}, IGFBP4 (insulin like growth factor binding protein 4) [NCBI Gene 3487] {aka BP-4, HT29-IGFBP, IBP4, IGFBP-4}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, IFIT1 (interferon induced protein with tetratricopeptide repeats 1) [NCBI Gene 3434] {aka C56, G10P1, IFI-56, IFI-56K, IFI56, IFIT-1}, STAT3 (signal transducer and activator of transcription 3) [NCBI Gene 6774] {aka ADMIO, ADMIO1, APRF, HIES}, XAF1 (XIAP associated factor 1) [NCBI Gene 54739] {aka BIRC4BP, HSXIAPAF1, XIAPAF1}
- **Diseases:** CCA (MESH:D018281), cancers (MESH:D009369)
- **Species:** Homo sapiens (human, species) [taxon 9606], Newcastle Disease Virus [taxon 11176]
- **Cell lines:** KKU-100 — Homo sapiens (Human), Hilar cholangiocarcinoma, Cancer cell line (CVCL_3996), KKU-055 — Homo sapiens (Human), Intrahepatic cholangiocarcinoma, Cancer cell line (CVCL_M258)

## Full text

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## Figures

3 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12054853/full.md

## References

53 references — full list in the complete paper: https://tomesphere.com/paper/PMC12054853/full.md

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Source: https://tomesphere.com/paper/PMC12054853