The circRNA DENND4C/miR-145-5p/HOXA9 Pathway Regulates Tumor Growth and Bone Metastasis in Breast Cancer

Abstract

BackgroundCircular RNAs (circRNAs) are involved in the occurrence and development of breast cancer bone metastasis. This study aims to identify whether the circRNA DENND4C/ miR145-5p/HOXA9 axis is involved in the regulation of cell invasion and migration and breast cancer progression.MethodscircRNA DENND4C, miR-145-5p and HOXA9 expression was measured in serum samples from healthy volunteers, breast cancer patients without bone metastasis and breast cancer patients with bone metastasis. Moreover, we analyzed the levels of circRNA DENND4C, miR‑145-5p and HOXA9 according to different conditions of differentiation, tumor volume and lymph node metastasis. The online software starBases and the dual-luciferase reporter gene assay were used to predict the relationship miR-145-5p, circRNA DENND4C and HOXA9 mRNA. MTT assays were performed to assess the effect of circRNA DENND4C on proliferation. To assess the proliferation of breast cancer cells among different groups. Statistical significance was determined byStudent's t‑test which was used for comparisons between two groups and one‑way analysis of variance followed by Tukey's post hoc test for comparisons between more than two groups.ResultsThe expression patterns of circRNA DENND4C, miR145-5p and HOXA9 were altered in patients with breast cancer bone metastasis. Notably, the stimulatory effects of circRNA DENND4C overexpression on HOXA9 were eliminated by miR-145-5p upregulation. circRNA DENND4C overexpression promotes proliferation, migration and invasiveness by regulating the miR-145-5p/HOXA9 axis. circRNA DENND4C downregulation suppresses proliferation, cell viability and invasiveness by regulating the miR-145-5p/HOXA9 axis. ConclusionOur study suggest that circRNA DENND4C/miR-145-5p/HOXA9 pathway was involved in tumor growth and bone metastasis in breast cancer. This findings may facilitate the development of potential therapeutic agents to improve the prognosis of patients with breast cancer bone metastasis.