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author：

Lai, Y. (Lai, Y..) [1] | Wang, F. (Wang, F..) [2] | Cai, G. (Cai, G..) [3] | Li, Y. (Li, Y..) [4] | Weng, J. (Weng, J..) [5] | Cai, F. (Cai, F..) [6] | Cai, L. (Cai, L..) [7] | Cheng, N. (Cheng, N..) [8] | Zhao, B. (Zhao, B..) [9] | Zeng, Y. (Zeng, Y..) [10]

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Scopus

Abstract：

Background:　Hepatocellular　carcinoma　(HCC)　is　characterized　by　a　complex　interplay　of　genetic　and　epigenetic　alterations　that　contribute　to　its　aggressive　nature　and　resistance　to　conventional　therapies.　The　recent　advent　of　immune　checkpoint　inhibitors　has　shown　promise　in　enhancing　the　immune　system＇s　ability　to　target　cancer　cells.　However,　the　efficacy　of　these　therapies　is　often　hindered　by　the　tumor＇s　immunosuppressive　microenvironment.　Circular　RNAs　(circRNAs),　a　class　of　non-coding　RNAs,　have　emerged　as　promising　candidates　for　the　development　of　novel　therapeutics　due　to　their　unique　properties,　including　resistance　to　degradation　and　the　ability　to　act　as　miRNA　sponges.　Methods:　In　this　study,　we　engineered　artificial　circRNAs　to　target　oncogenic　miRNAs　and　to　express　anti-PD-1　scFv　antibodies,　aiming　to　simultaneously　disrupt　oncogenic　pathways　and　enhance　the　immune　response　against　HCC.　Results:　Our　results　demonstrate　that　the　engineered　circRNAs　effectively　sponge　miR-25,　leading　to　subsequent　inhibition　of　HCC　cell　proliferation　and　angiogenesis.　Moreover,　the　expression　of　anti-PD-1　scFv　antibodies　from　the　circRNAs　significantly　enhanced　the　cytotoxic　T-cell　response　against　HCC　cells.　In　vivo　studies　revealed　a　significant　reduction　in　tumor　volume　and　prolonged　survival　in　mice　treated　with　the　engineered　circRNAs　compared　to　controls.　Conclusions:　Our　findings　highlight　the　potential　of　artificial　circRNAs　as　a　novel　therapeutic　strategy　for　HCC.　By　harnessing　their　ability　to　act　as　miRNA　sponges　and　to　express　immunomodulatory　proteins,　these　engineered　circRNAs　offer　a　promising　approach　to　overcome　the　challenges　associated　with　HCC　therapy.　Copyright　©　2025　Lai,　Wang,　Cai,　Li,　Weng,　Cai,　Cai,　Cheng,　Zhao　and　Zeng.

Keyword：

anti-PD-1 circular RNA hepatocellular carcinoma immunotherapy miRNA sponge scFv antibody

Community：

  • [ 1 ] [Lai Y.]Department of Hepatopancreatobiliary Surgery, First Affiliated Hospital of Fujian Medical University, Fuzhou, China
  • [ 2 ] [Lai Y.]Department of Hepatobiliary Pancreatic Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fujian, Fuzhou, China
  • [ 3 ] [Wang F.]The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, China
  • [ 4 ] [Wang F.]Mengchao Med-X Center, Fuzhou University, Fuzhou, China
  • [ 5 ] [Cai G.]The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, China
  • [ 6 ] [Cai G.]Mengchao Med-X Center, Fuzhou University, Fuzhou, China
  • [ 7 ] [Li Y.]The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, China
  • [ 8 ] [Li Y.]Mengchao Med-X Center, Fuzhou University, Fuzhou, China
  • [ 9 ] [Weng J.]The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, China
  • [ 10 ] [Cai F.]The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, China
  • [ 11 ] [Cai F.]Mengchao Med-X Center, Fuzhou University, Fuzhou, China
  • [ 12 ] [Cai L.]The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, China
  • [ 13 ] [Cai L.]Mengchao Med-X Center, Fuzhou University, Fuzhou, China
  • [ 14 ] [Cheng N.]The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, China
  • [ 15 ] [Cheng N.]Mengchao Med-X Center, Fuzhou University, Fuzhou, China
  • [ 16 ] [Zhao B.]The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, China
  • [ 17 ] [Zhao B.]Mengchao Med-X Center, Fuzhou University, Fuzhou, China
  • [ 18 ] [Zeng Y.]Department of Hepatopancreatobiliary Surgery, First Affiliated Hospital of Fujian Medical University, Fuzhou, China
  • [ 19 ] [Zeng Y.]Department of Hepatobiliary Pancreatic Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fujian, Fuzhou, China
  • [ 20 ] [Zeng Y.]The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, China
  • [ 21 ] [Zeng Y.]Mengchao Med-X Center, Fuzhou University, Fuzhou, China

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Frontiers in Immunology

ISSN： 1664-3224

Year： 2025

Volume： 16

5 . 7 0 0

JCR@2023

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ESI Highly Cited Papers on the List： 0 Unfold All

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