CircRNA has_circ_0069313 induced OSCC immunity escape by miR-325-3p-Foxp3 axes in both OSCC cells and Treg cells

Aging (Albany NY). 2022 May 16;14(10):4376-4389. doi: 10.18632/aging.204068. Epub 2022 May 16.


Introduction: CircRNAs are engaged in the tumorigenesis and progression of oral squamous cancer cells (OSCC). However, the function and underlying mechanism of circRNAs on tumor-associated immunity escape are largely unknown.

Materials and methods: We analyzed the expression pattern of has_circ_0069313 in our in-house database and its correlation with OSCC prognosis. Immunohistochemistry was applied to detected PDL1 expression. RNA fluorescence in situ hybridization was applied to detect subcellular location of circRNA. A luciferase activity assay was used to detect the interaction of has_circ_0069313 and miR-325-3p and its downstream target, Foxp3. Exosomes were collected to detect the exosomal circRNAs and co-culture assays were performed to detect the function of exosomal circRNAs on Tregs.

Results: has_circ_0069313 was upregulated in OSCC tissues and predicts poor prognosis. has_circ_0069313 promotes immunity escape through inhibiting miR-325-3p-induced Foxp3 degradation. has_circ_0069313 is an exosomal circRNA and the transfer of has_circ_0069313 to Treg cells promotes the Treg function through maintaining Foxp3 levels.

Conclusion: Our results indicate that has_circ_0069313 induces OSCC immunity escape via the miR-325-3p-Foxp3 axis in both OSCC cells and Treg cells.

Keywords: OSCC; PDL1; Treg; cancer immunity; circRNA.

MeSH terms

  • Cell Proliferation
  • Forkhead Transcription Factors / genetics
  • Forkhead Transcription Factors / metabolism
  • Gene Expression Regulation, Neoplastic
  • Humans
  • In Situ Hybridization, Fluorescence
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Mouth Neoplasms* / metabolism
  • RNA, Circular / genetics
  • T-Lymphocytes, Regulatory / metabolism
  • Transcription Factors / metabolism


  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • MIRN325 microRNA, human
  • MicroRNAs
  • RNA, Circular
  • Transcription Factors