Circular forms of dedicator of cytokinesis 1 promotes breast cancer progression by derepressing never in mitosis related kinase 2 via sponging miR‐128‐3p

Abstract

AbstractThe conjecture of breast cancer is uncertain because of its explosive growth and the complicated molecular mechanisms. Circular RNAs (circRNAs) are regulatory RNA sequences present in the genome and their regulatory mechanism involves the sponging of microRNAs (miRNAs). In this study, we explored the regulation between circular forms of dedicator of cytokinesis 1 (circDOCK1) (hsa_circ_0007142) and miR‐128‐3p, and its implication on the pathogenesis of breast cancer modulated by never in mitosis (NIMA) related kinase 2 (NEK2). We revealed an increase in circDOCK1 and NEK2 expression, and a decrease in miR‐128‐3p expression in breast cancer tissues and cell lines. Bioinformatics analysis and experimental validation indicated a positive correlation between circDOCK1 and NEK2 expression but a negative correlation was recorded between miR‐128‐3p and circDOCK1 or NEK2, respectively. Furthermore, inhibition of circDOCK1 expression was followed by an increase in miR‐128‐3p and a decrease in NEK2 levels in vitro and in vivo. The luciferase assay concluded that miR‐128‐3p was a direct target of circDOCK1 while NEK2 was the direct target of miR‐128‐3p. Furthermore, circDOCK1 inhibition hindered breast cancer development by repressing NEK2 and thus promoting the increased expression of miR‐128‐3p both in vitro and in vivo. We therefore conclude that circDOCK1 promotes breast cancer progression by targeting miR‐128‐3p‐mediated downregulation of NEK2 and that the circDOCK1/hsa‐miR‐128‐3p/NEK2 axis may be a novel therapeutic target for breast cancer treatment.