MicroRNA-4521 targets hepatoma up-regulated protein (HURP) to inhibit the malignant progression of breast cancer

Abstract

ABSTRACT Breast cancer (BC) is a common malignancy among women, and microRNAs (miRNAs) play a role in its progression. Reportedly, microRNA-4521 (miR-4521) participates in regulating the progression of some carcinomas. In the present work, miR-4521 and hepatoma up-regulated protein (HURP) mRNA expressions in BC tissues and cell lines were examined by qRT-PCR. After miR-4521 was overexpressed or knocked down in BC cells, CCK-8 experiment and EdU experiment were employed to detect BC cell growth. Moreover, the Transwell assay was adopted to detect the migration and invasion. Subsequently, flow cytometry was executed to evaluate the changes in cell cycle progression. KEGG analysis was utilized to predict the signaling pathways related with the target genes of miR-524-5p. The binding relationship between miR-4521 and HURP 3ʹUTR was validated by dual-luciferase reporter gene experiment. HURP and NF-kB p65 protein expression in BC cells was detected by Western blot. It was revealed that, miR-4521 was lowly expressed in BC tissues, and its expression was associated with tumor grade, lymph node metastasis and clinical stage of the patients. Overexpression of miR-4521 suppressed the growth, migration, invasion and cell cycle progression of BC cells and restrained p65 expression; downregulation of miR-4521 in BC cells showed opposite biological effects. Additionally, HURP was a downstream target gene of miR-4521, and overexpression of HURP reversed the above effects of miR-4521 overexpression. In short, miR-4521 can inhibit BC progression by modulating the HURP/NF-κB pathway.