Circ-RNF111 contributes to paclitaxel resistance in breast cancer by elevating E2F3 expression via miR-140-5p

Abstract

Background: Circular RNAs (circRNAs) have been demonstrated to act as key regulators in the chemoresistance of human cancers, including breast cancer (BC). Here, we aimed to explore the role of circ-RNF111 in paclitaxel (PTX) resistance of BC. Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) was employed to determine the expression of circ-RNF111, microRNA-140-5p (miR-140-5p) and E2F transcription factor 3 (E2F3) mRNA. The half maximal inhibitory concentration (IC50) of PTX, cell viability, colony formation and cell invasion were assessed by cell counting kit-8 (CCK-8) assay, colony formation assay and transwell assay, respectively. Glucose consumption and lactate production were determined by specific kits. A murine xenograft model was established to investigate the role of circ-RNF111 in PTX resistance of BC in vivo. Dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were performed to verify the relationship between miR-140-5p and circ-RNF111 or E2F3. Western blot assay was conducted to examine the protein level of E2F3. Results: Circ-RNF111 was upregulated in PTX-resistant BC tissues and cells. Circ-RNF111 knockdown restrained IC50 of PTX, cell viability, colony numbers, cell invasion and glycolysis in PTX-resistant BC cells in vitro and enhanced PTX sensitivity in vivo. MiR-140-5p was a target of circ-RNF111 and miR-140-5p expression was negatively correlated with circ-RNF111 expression in BC tissues. The effect of circ-RNF111 knockdown on PTX resistance was rescued by miR-140-5p deletion. Additionally, miR-140-5p could interact with E2F3 and negatively regulate E2F3 expression. Moreover, miR-140-5p suppressed IC50 of PTX, cell viability, colony numbers, cell invasion and glycolysis by targeting E2F3. Conclusions: Circ-RNF111 improved PTX resistance of BC by upregulating E2F3 via sponging miR-140-5p.