circ-1584 selectively promotes the antitumor activity of the oncolytic virus M1 on pancreatic cancer

Pancreatic cancer is among the most challenging tumors to treat, and due to its immune tolerance characteristics, existing immunotherapy methods are not effective in alleviating the disease. Oncolytic virus therapy, a potential new strategy for treating pancreatic cancer, also faces the limitation o...

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Main Authors: Taofang Hao, Yuanyuan Li, Qianyao Ren, Ying Zeng, Leyi Gao, Wenbo Zhu, Jiankai Liang, Yuan Lin, Jun Hu, Guangmei Yan, Shuxin Sun, Jing Cai
Format: Article
Language:English
Published: Elsevier 2025-03-01
Series:Molecular Therapy: Oncology
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Online Access:http://www.sciencedirect.com/science/article/pii/S2950329924001619
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author Taofang Hao
Yuanyuan Li
Qianyao Ren
Ying Zeng
Leyi Gao
Wenbo Zhu
Jiankai Liang
Yuan Lin
Jun Hu
Guangmei Yan
Shuxin Sun
Jing Cai
author_facet Taofang Hao
Yuanyuan Li
Qianyao Ren
Ying Zeng
Leyi Gao
Wenbo Zhu
Jiankai Liang
Yuan Lin
Jun Hu
Guangmei Yan
Shuxin Sun
Jing Cai
author_sort Taofang Hao
collection DOAJ
description Pancreatic cancer is among the most challenging tumors to treat, and due to its immune tolerance characteristics, existing immunotherapy methods are not effective in alleviating the disease. Oncolytic virus therapy, a potential new strategy for treating pancreatic cancer, also faces the limitation of being ineffective when used alone. Elucidating the key host endogenous circular RNAs (circRNAs) involved in M1 virus-mediated killing of pancreatic ductal adenocarcinoma (PDAC) cells may help overcome this limitation. Here, we report that the oncolytic virus M1, a nonpathogenic alphavirus, exhibits different cell viability-inhibitory effects on different pancreatic cancer cells in the clinical stage. Through high-throughput circRNA sequencing, we found that circRNA expression varies among these cells. Further gain-of-function and loss-of-function experiments have shown that circ-1584 can selectively enhance the anti-pancreatic cancer effects of the M1 virus in vitro and in vivo. Additionally, circ-1584 may negatively regulate miR-578 to modulate the anti-pancreatic cancer effects of the M1 virus. Our findings lay the foundation for using circRNA as an adjuvant to enhance the M1 virus efficacy against pancreatic cancer.
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issn 2950-3299
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publishDate 2025-03-01
publisher Elsevier
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series Molecular Therapy: Oncology
spelling doaj-art-10c7bbbe613a4a50b70db8bd985d5fda2025-01-08T04:53:56ZengElsevierMolecular Therapy: Oncology2950-32992025-03-01331200919circ-1584 selectively promotes the antitumor activity of the oncolytic virus M1 on pancreatic cancerTaofang Hao0Yuanyuan Li1Qianyao Ren2Ying Zeng3Leyi Gao4Wenbo Zhu5Jiankai Liang6Yuan Lin7Jun Hu8Guangmei Yan9Shuxin Sun10Jing Cai11Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, ChinaDepartment of Pharmacology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, ChinaDepartment of Pharmacology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, ChinaDepartment of Pharmacology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, ChinaDepartment of Pharmacology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, ChinaDepartment of Pharmacology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, ChinaDepartment of Pharmacology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, ChinaDepartment of Pharmacology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China; Advanced Medical Technology Center, The First Affiliated Hospital-Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China; Key Laboratory of Human Microbiome and Elderly Chronic Diseases, Ministry of Education, Beijing, ChinaDepartment of Pharmacology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, ChinaDepartment of Pharmacology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, ChinaPancreatic Center, Guangdong Provincial People’s Hospital, Guangzhou, China; Corresponding author: ShuXin Sun, Pancreatic Center, Guangdong Provincial People's Hospital, Guangzhou 510080, China.Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China; Department of Molecular Biology and Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China; Corresponding author: Jing Cai, Department of Molecular Biology and Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.Pancreatic cancer is among the most challenging tumors to treat, and due to its immune tolerance characteristics, existing immunotherapy methods are not effective in alleviating the disease. Oncolytic virus therapy, a potential new strategy for treating pancreatic cancer, also faces the limitation of being ineffective when used alone. Elucidating the key host endogenous circular RNAs (circRNAs) involved in M1 virus-mediated killing of pancreatic ductal adenocarcinoma (PDAC) cells may help overcome this limitation. Here, we report that the oncolytic virus M1, a nonpathogenic alphavirus, exhibits different cell viability-inhibitory effects on different pancreatic cancer cells in the clinical stage. Through high-throughput circRNA sequencing, we found that circRNA expression varies among these cells. Further gain-of-function and loss-of-function experiments have shown that circ-1584 can selectively enhance the anti-pancreatic cancer effects of the M1 virus in vitro and in vivo. Additionally, circ-1584 may negatively regulate miR-578 to modulate the anti-pancreatic cancer effects of the M1 virus. Our findings lay the foundation for using circRNA as an adjuvant to enhance the M1 virus efficacy against pancreatic cancer.http://www.sciencedirect.com/science/article/pii/S2950329924001619MT: Regular IssuePDACcircRNAoncolytic virusM1
spellingShingle Taofang Hao
Yuanyuan Li
Qianyao Ren
Ying Zeng
Leyi Gao
Wenbo Zhu
Jiankai Liang
Yuan Lin
Jun Hu
Guangmei Yan
Shuxin Sun
Jing Cai
circ-1584 selectively promotes the antitumor activity of the oncolytic virus M1 on pancreatic cancer
Molecular Therapy: Oncology
MT: Regular Issue
PDAC
circRNA
oncolytic virus
M1
title circ-1584 selectively promotes the antitumor activity of the oncolytic virus M1 on pancreatic cancer
title_full circ-1584 selectively promotes the antitumor activity of the oncolytic virus M1 on pancreatic cancer
title_fullStr circ-1584 selectively promotes the antitumor activity of the oncolytic virus M1 on pancreatic cancer
title_full_unstemmed circ-1584 selectively promotes the antitumor activity of the oncolytic virus M1 on pancreatic cancer
title_short circ-1584 selectively promotes the antitumor activity of the oncolytic virus M1 on pancreatic cancer
title_sort circ 1584 selectively promotes the antitumor activity of the oncolytic virus m1 on pancreatic cancer
topic MT: Regular Issue
PDAC
circRNA
oncolytic virus
M1
url http://www.sciencedirect.com/science/article/pii/S2950329924001619
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