AI Article Synopsis

  • Scientists found that a special type of small circular RNA called circ_0001947, which comes from gastric cancer cells, can make cancer worse and reduce the body’s immune response against the cancer.
  • They used different experiments to see how this circRNA affects cancer cells and immune cells, discovering that it helps cancer cells grow and move around by affecting other molecules in the body.
  • The study suggests that targeting this circRNA might help improve treatments for gastric cancer by boosting the immune system's ability to fight the cancer.

Article Abstract

Background: While small extracellular vesicles (sEVs)-derived circular RNAs (circRNAs) have been emerged as significant players in cancer, the function and underlying mechanism of sEVs-derived circRNAs in anti-cancer immunity remain unclear.

Methods: Gastric cancer (GC)-derived circRNAs were identified using RNA-seq data from GEO datasets and quantitative reverse transcription polymerase chain reaction (qRT-PCR), RNA immunoprecipitation, dual-luciferase assay, and bioinformatics analysis were performed to investigate the regulatory axis. Transwell assay, wound healing assay, cell counting kit-8 (CCK-8) assay, and xenograft models were used to evaluate its role in GC progression in vivo and in vitro. The delivery of specific circRNAs into sEVs were verified through electron microscopy, nanoparticle tracking analysis (NTA) and fuorescence in situ hybridization (FISH). Flow cytometric analysis and immunohistochemical staining were conducted to find out how specific circRNAs mediated CD8 T cell exhaustion and resistant to anti-programmed cell death 1 (PD-1) therapy.

Results: We identified that circ_0001947, packaged by GC-derived sEVs, was obviously elevated in GC and was associated with poor clinical outcome. High circ0001947 level augmented the proliferation, migration, and invasion of GC cells. Mechanistically, circ0001947 sponged miR-661 and miR-671-5p to promote the expression of CD39, which further facilitated CD8 T cell exhaustion and immune resistance. Conversely, blocking circ_0001947 attenuated CD8 T cell exhaustion and increased the response to anti-PD-1 therapy.

Conclusions: Our study manifested the therapeutic potential of targeting sEVs-transmitted circ_0001947 to prohibit CD8 T cell exhaustion and immune resistance in GC.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11401313PMC
http://dx.doi.org/10.1186/s12951-024-02826-5DOI Listing

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