CircZFR promotes colorectal cancer progression via stabilizing BCLAF1 and regulating the miR-3127-5p/RTKN2 axis

Aberrant expression of circular RNAs(circ RNAs)is frequently linked to colorectal cancer(CRC).Here,we identified circ ZFR as a promising biomarker for CRC diagnosis and prognosis.Circ ZFR was upregulated in CRC tissues and serum exosomes and its level was linked to cancer incidence,advanced-stages,and metastasis.In both in vitro and in vivo settings,circ ZFR promoted the growth and spread while suppressing apoptosis of CRC.Exosomes with circ ZFR overexpression promoted the proliferation and migration of cocultured CRC cells.Mechanistically,epithelial splicing regulatory protein 1(ESRP1)in CRC cells may enhance the production of circ ZFR.BCL2-associated transcription factor 1(BCLAF1)bound to circ ZFR,which prevented its ubiquitinated degradation.Additionally,circ ZFR sponged mi R-3127-5p to boost rhotekin 2(RTKN2)expression.Our TCP1-CD-QDs nanocarrier was able to carry and deliver circ ZFR si RNA(si-circ ZFR)to the vasculature of CRC tissues and cells,which inhibited the growth of tumors in patient-derived xenograft(PDX)models.Taken together,our results show that circ ZFR is an oncogenic circ RNA,which promotes the development and spread of CRC in a BCLAF1 and mi R-3127-5p-dependent manner.Circ ZFR is a possible serum biopsy marker for the diagnosis and a desirable target for further treatment of CRC.