circREEP3 Drives Colorectal Cancer Progression via Activation of FKBP10 Transcription and Restriction of Antitumor Immunity

Adv Sci (Weinh). 2022 May;9(13):e2105160. doi: 10.1002/advs.202105160. Epub 2022 Mar 1.


Colorectal cancer (CRC) is one of the most common tumors around the world. Circular RNA is widely involved in tumor progression via unclear mechanisms. Here, circREEP3 is found to be upregulated in CRC tissues. circREEP3 upregulation predicts poor patient survival. circREEP3 knockout suppresses CRC tumorigenesis and metastasis, and impairs stem cell-like phenotype. Mechanistically, circREEP3 recruits the chromatin remodeling protein CHD7 to FKBP10 promoter and activates its transcription. Moreover, circREEP3 restricts RIG-1-dependent antitumor immunity. FKBP10 is highly expressed in CRC tissues and associated with poor prognosis. FKBP10 ectopic expression partially rescues the potential of proliferation and metastasis in circREEP3-deficient CRC cells. Thus, the findings support circREEP3-FKBP10 axis drives CRC progression and may be a critical prognostic marker.

Keywords: FKBP10; antitumor immunity; circREEP3; colorectal cancer.

MeSH terms

  • Carcinogenesis / genetics
  • Cell Proliferation / genetics
  • Colorectal Neoplasms* / genetics
  • Colorectal Neoplasms* / metabolism
  • Colorectal Neoplasms* / pathology
  • Gene Expression Regulation, Neoplastic* / genetics
  • Humans
  • RNA, Circular / genetics
  • Tacrolimus Binding Proteins / genetics
  • Tacrolimus Binding Proteins / metabolism


  • RNA, Circular
  • Tacrolimus Binding Proteins
  • FKBP10 protein, human