Upregulated Circular RNA circ-UBE2D2 Predicts Poor Prognosis and Promotes Breast Cancer Progression by Sponging miR-1236 and miR-1287

Abstract

Emerging evidence suggests that circular RNAs (circRNAs) are linked to the development and progression of human cancers. Nevertheless, their contribution to breast cancer (BC) is still largely unknown. In the current study, we screened and identified a novel circRNA, circ-UBE2D2, which was highly expressed in BC cell lines and tissues and was closely related to aggressive clinical features and dismal prognosis. Small interfering RNA (siRNA)–mediated circ-UBE2D2 silencing notably inhibited the proliferation, migration and invasion of BC cells, whereas circ-UBE2D2 overexpression displayed opposite effects. Mechanistically, circ-UBE2D2 was able to simultaneously function as molecular sponges of miR-1236 and miR-1287 to regulate the expression of their respective target genes. Moreover, circ-UBE2D2–induced tumor-promoting effects could be effectively blocked by miR-1236 or miR-1287 in BC cells. More importantly, therapeutic delivery of cholesterol-conjugated si-circ-UBE2D2 oligonucleotides significantly delayed tumor growth in vivo. Overall, our findings indicate that circ-UBE2D2 plays an essential oncogenic role in BC, and targeting circ-UBE2D2 may be a feasible treatment for BC patients.