Circ-EEF2 facilitated autophagy via interaction with mir-6881-3p and ANXA2 in EOC

Am J Cancer Res. 2020 Nov 1;10(11):3737-3751. eCollection 2020.

Abstract

Circular RNAs, a special class of non-coding RNA with closed circular structure, have been increasingly proven to be involved in the progression of various tumors. However, the biological functions of circular RNAs in epithelial ovarian cancer (EOC) tissues remain a mystery. In this study, we detected the function of circEEF2 (has-circ-0048559) in EOC tissues. Firstly, the basic characteristics including closed circular structure and spliced mature sequence length of circEEF2 were confirmed. The location and expression in EOC tissues was detected by fluorescence in situ hybridization (FISH). The regulatory effect of circEEF2 on autophagy, proliferation, and invasion were investigated in SKOV3 and A2780 cells. The relationship between circEEF2 and mir-6881-3p was confirmed using dual-luciferase reporter gene assay. The binding of circEEF2 with ANXA2 was confirmed using RNA-pulldown assay and MALDI-TOF-MS. We found that the expression level of circEEF2 was higher in EOC tissue than in normal tissue. CircEEF2 promoted autophagy, proliferation, and invasion. CircEEF2-regulated EOC proliferation and invasion are closely related to the occurrence of autophagy. Mechanistically, circEEF2 harbor miR-6881-3p to upregulate the latter's targets ATG5 and ATG7. Moreover, circEEF2 could directly bind with ANXA2 to inhibit the expression of p-mTOR. In conclusion, findings of the current study illustrate that circEEF2 promoted autophagy, proliferation, and invasion of EOC by interacting with miR-6881-3p and ANXA2.

Keywords: ANXA2; autophagy; circEEF2; epithelial ovarian cancer; miR-6881-3P.