Adeno-associated virus mediated artificial circular RNA for triggering cancer immunotherapy to treat prostate cancer

IntroductionSpecifically regulating endogenous molecules is a potential molecular therapeutic strategy. Naturally occurring circular RNAs (circRNAs) are structurally stable and have been proved to serve as highly efficient miR-sponges and protein-sponges in cancer cells.MethodsWe chemically synthesi...

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Main Authors: Chujin Ye, Zhiye Liu, Qifan Xie, Yanlin Tang, Jiayi Zeng, Ziwei Feng, Jiumin Liu, Haibiao Xie
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-01-01
Series:Frontiers in Oncology
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Online Access:https://www.frontiersin.org/articles/10.3389/fonc.2025.1443571/full
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author Chujin Ye
Chujin Ye
Zhiye Liu
Zhiye Liu
Qifan Xie
Qifan Xie
Yanlin Tang
Yanlin Tang
Jiayi Zeng
Jiayi Zeng
Ziwei Feng
Ziwei Feng
Jiumin Liu
Jiumin Liu
Haibiao Xie
Haibiao Xie
author_facet Chujin Ye
Chujin Ye
Zhiye Liu
Zhiye Liu
Qifan Xie
Qifan Xie
Yanlin Tang
Yanlin Tang
Jiayi Zeng
Jiayi Zeng
Ziwei Feng
Ziwei Feng
Jiumin Liu
Jiumin Liu
Haibiao Xie
Haibiao Xie
author_sort Chujin Ye
collection DOAJ
description IntroductionSpecifically regulating endogenous molecules is a potential molecular therapeutic strategy. Naturally occurring circular RNAs (circRNAs) are structurally stable and have been proved to serve as highly efficient miR-sponges and protein-sponges in cancer cells.MethodsWe chemically synthesized circRNA (ScircRNA) in vitro to achieve therapeutic dysfunction by targeting specific miRNAs. RNase R and fetal bovine serum were used to evaluate the stability of ScircRNAs. In prostate cancer cell lines, the competitive inhibition of the ScircRNA on miR-375 and miR-21 activity was evaluated using luciferase report gene, cell proliferation, and apoptosis assays.ResultsWe found that ScircRNAs were more resistant to nuclease digestion and more effective inhibiting target miRNAs than linear RNA sponges. The ScircRNAs inhibited malignant phenotype of prostate cancer by specifically inhibiting the activity of miR-21 and miR-375. In addition, we used the ScircRNA inhibiting CDK5 expression to trigger T-cell mediated cancer immunotherapy for treating prostate cancer in vivo.DiscussionThe ScircRNAs possessed the advantages of stable structure and simple construction, and can specifically inhibit the function of target miRNAs, which has a potential therapeutic application prospect in prostate cancer.
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institution Kabale University
issn 2234-943X
language English
publishDate 2025-01-01
publisher Frontiers Media S.A.
record_format Article
series Frontiers in Oncology
spelling doaj-art-654388200999460fb28fb879fdb859032025-01-31T06:40:04ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2025-01-011510.3389/fonc.2025.14435711443571Adeno-associated virus mediated artificial circular RNA for triggering cancer immunotherapy to treat prostate cancerChujin Ye0Chujin Ye1Zhiye Liu2Zhiye Liu3Qifan Xie4Qifan Xie5Yanlin Tang6Yanlin Tang7Jiayi Zeng8Jiayi Zeng9Ziwei Feng10Ziwei Feng11Jiumin Liu12Jiumin Liu13Haibiao Xie14Haibiao Xie15Department of Urology, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, ChinaThe Second School of Clinical Medicine, Southern Medical University, Guangzhou, ChinaDepartment of Urology, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, ChinaThe Second School of Clinical Medicine, Southern Medical University, Guangzhou, ChinaDepartment of Urology, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, ChinaThe Second School of Clinical Medicine, Southern Medical University, Guangzhou, ChinaDepartment of Urology, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, ChinaThe Second School of Clinical Medicine, Southern Medical University, Guangzhou, ChinaDepartment of Urology, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, ChinaThe Second School of Clinical Medicine, Southern Medical University, Guangzhou, ChinaDepartment of Urology, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, ChinaThe Second School of Clinical Medicine, Southern Medical University, Guangzhou, ChinaDepartment of Urology, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, ChinaThe Second School of Clinical Medicine, Southern Medical University, Guangzhou, ChinaDepartment of Urology, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, ChinaThe Second School of Clinical Medicine, Southern Medical University, Guangzhou, ChinaIntroductionSpecifically regulating endogenous molecules is a potential molecular therapeutic strategy. Naturally occurring circular RNAs (circRNAs) are structurally stable and have been proved to serve as highly efficient miR-sponges and protein-sponges in cancer cells.MethodsWe chemically synthesized circRNA (ScircRNA) in vitro to achieve therapeutic dysfunction by targeting specific miRNAs. RNase R and fetal bovine serum were used to evaluate the stability of ScircRNAs. In prostate cancer cell lines, the competitive inhibition of the ScircRNA on miR-375 and miR-21 activity was evaluated using luciferase report gene, cell proliferation, and apoptosis assays.ResultsWe found that ScircRNAs were more resistant to nuclease digestion and more effective inhibiting target miRNAs than linear RNA sponges. The ScircRNAs inhibited malignant phenotype of prostate cancer by specifically inhibiting the activity of miR-21 and miR-375. In addition, we used the ScircRNA inhibiting CDK5 expression to trigger T-cell mediated cancer immunotherapy for treating prostate cancer in vivo.DiscussionThe ScircRNAs possessed the advantages of stable structure and simple construction, and can specifically inhibit the function of target miRNAs, which has a potential therapeutic application prospect in prostate cancer.https://www.frontiersin.org/articles/10.3389/fonc.2025.1443571/fullprostate cancermiRNAcircRNAcancer immunotherapysynthetic biology
spellingShingle Chujin Ye
Chujin Ye
Zhiye Liu
Zhiye Liu
Qifan Xie
Qifan Xie
Yanlin Tang
Yanlin Tang
Jiayi Zeng
Jiayi Zeng
Ziwei Feng
Ziwei Feng
Jiumin Liu
Jiumin Liu
Haibiao Xie
Haibiao Xie
Adeno-associated virus mediated artificial circular RNA for triggering cancer immunotherapy to treat prostate cancer
Frontiers in Oncology
prostate cancer
miRNA
circRNA
cancer immunotherapy
synthetic biology
title Adeno-associated virus mediated artificial circular RNA for triggering cancer immunotherapy to treat prostate cancer
title_full Adeno-associated virus mediated artificial circular RNA for triggering cancer immunotherapy to treat prostate cancer
title_fullStr Adeno-associated virus mediated artificial circular RNA for triggering cancer immunotherapy to treat prostate cancer
title_full_unstemmed Adeno-associated virus mediated artificial circular RNA for triggering cancer immunotherapy to treat prostate cancer
title_short Adeno-associated virus mediated artificial circular RNA for triggering cancer immunotherapy to treat prostate cancer
title_sort adeno associated virus mediated artificial circular rna for triggering cancer immunotherapy to treat prostate cancer
topic prostate cancer
miRNA
circRNA
cancer immunotherapy
synthetic biology
url https://www.frontiersin.org/articles/10.3389/fonc.2025.1443571/full
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