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

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.

Keywords: Bladder cancer; IL-6; Immune evasion; JAK/STAT; Proliferation; circFAM64A.