Circ-E2F3 promotes cervical cancer progression by inhibiting microRNA-296-5p and increasing STAT3 nuclear translocation

Circular RNA E2F transcription factor 3 (circ-E2F3) has been demonstrated to be differentially expressed in some diseases and cancers. However, the role of circ-E2F3 in cervical cancer (CC) progression remains unclear. Therefore, we aimed to elucidate the mechanism of circ-E2F3 regulation of CC progression. Circ-E2F3 expression was determined in CC samples, and its correlation with the clinicopathological characteristics of CC patients and cell biological processes was examined. The interaction among circ-E2F3, microRNA-296-5p (miR-296-5p), and signal transducer and activator of transcription 3 (STAT3) was analyzed by dual luciferase reporter gene and fluorescence in situ hybridization assays. Circ-E2F3-depleted CaSki cells were implanted into nude mice to verify the function of circ-E2F3 in vivo. Circ-E2F3 was upregulated in both CC tissues and cell lines, and this correlated with the clinicopathological features and poor prognosis of CC patients. Moreover, circ-E2F3 promoted the proliferation, invasion, and migration of CC cells and tumor growth in vivo. It was also observed that circ-E2F3 promoted the nuclear translocation of STAT3 through inhibition of miR-296-5p, thus affecting the expression of cyclin D1. Taken together, the key findings of our study demonstrate that circ-E2F3 induces inhibition of miR-296-5p, which triggers activation and nuclear translocation of STAT3 that then upregulates cyclin D1 expression.

Automated summary

Circ-E2F3 is upregulated in cervical cancer tissues and cell lines, correlating with clinicopathological features and poor prognosis of patients. It promotes proliferation, invasion, migration of cancer cells, and tumor growth in vivo, by inhibiting miR-296-5p to facilitate nuclear translocation of STAT3 and affect cyclin D1 expression.