CircFAM64A(3) promoted bladder cancer proliferation and inhibited CD8 + T cell via sponging to miR-149-5p and activated IL-6/JAK/STAT pathway.

IF 4.8 2区医学 Q2 IMMUNOLOGY

International immunopharmacology Pub Date : 2024-12-10 DOI:10.1016/j.intimp.2024.113762

Juntao Zhuang, Ming Zhou, Hao Yu, Rui Zhou, Kexin Bai, Jiancheng Lv, Kai Li, Yidong Cheng, Haiwei Yang, Xiao Yang, Qiang Lu

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引用次数: 0

Abstract

Background: The significance of circular RNA in tumour biology is increasingly recognized. This study aims to explore the value of circFAM64A(3) in the proliferation and immune evasion of bladder cancer.

Methods: Bioinformatics were used to identify the differentially expressed circular RNAs in bladder cancer. Proliferation assay, co-culture assay and flow cytometry assay confirmed the oncogenic and immune-evading characteristics of circFAM64A(3) in bladder cancer in vitro and in vivo. Further, mRNA sequencing, RNA pulldown, and RNA immunoprecipitation were used to confirm the downstream targets and pathways regulated by circFAM64A(3). CUT&TAG assay confirmed HIF-1α promoted the expression of circFAM64A(3) under hypoxic.

Results: CircFAM64A(3) was significantly high expression in bladder cancer tissues and related with poor prognosis of bladder cancer patients. CircFAM64A(3) promoted bladder cancer cells proliferation and immune evasion in vitro and in vivo. Mechanistically, circFAM64A(3) acted as a sponge to miR-149-5p and reduced the binding of miR-149-5p to IL-6 3'-UTR. Then, IL-6 activated the JAK/STAT pathway and caused an increase of PD-L1. Under hypoxic environment, HIF-1α bound to the promoter of FAM64A and promoted circFAM64A(3) transcription.

Conclusion: HIF-1α/circFAM64A(3)/miR-149-5p/IL-6 axis was an important regulatory pathway in bladder cancer proliferation and immune evasion. CircFAM64A(3) may serve as a novel and potentially valuable biological target.

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来源期刊

International immunopharmacology 医学-免疫学

CiteScore

8.40

自引率

3.60%

发文量

935

审稿时长

53 days

期刊介绍： International Immunopharmacology is the primary vehicle for the publication of original research papers pertinent to the overlapping areas of immunology, pharmacology, cytokine biology, immunotherapy, immunopathology and immunotoxicology. Review articles that encompass these subjects are also welcome. The subject material appropriate for submission includes: • Clinical studies employing immunotherapy of any type including the use of: bacterial and chemical agents; thymic hormones, interferon, lymphokines, etc., in transplantation and diseases such as cancer, immunodeficiency, chronic infection and allergic, inflammatory or autoimmune disorders. • Studies on the mechanisms of action of these agents for specific parameters of immune competence as well as the overall clinical state. • Pre-clinical animal studies and in vitro studies on mechanisms of action with immunopotentiators, immunomodulators, immunoadjuvants and other pharmacological agents active on cells participating in immune or allergic responses. • Pharmacological compounds, microbial products and toxicological agents that affect the lymphoid system, and their mechanisms of action. • Agents that activate genes or modify transcription and translation within the immune response. • Substances activated, generated, or released through immunologic or related pathways that are pharmacologically active. • Production, function and regulation of cytokines and their receptors. • Classical pharmacological studies on the effects of chemokines and bioactive factors released during immunological reactions.