MicroRNA-211, a direct negative regulator of CDC25B expression, inhibits triple-negative breast cancer cells' growth and migration.

Abstract

The non-coding microRNAs (miRNAs) have tissue- and disease-specific expression patterns. Dysregulation of miRNAs has been associated with initiation and progression of oncogenesis in humans. The abnormal expression of CDC25B phosphatases detected in a number of tumors implies that their dysregulation is involved in malignant transformation. Using miRNA target prediction software, we found that miR-211 could target the 3'UTR sequence of CDC25B. To shed light on their roles of miR-211 in breast cancer, the expression of miR-211 was examined by real-time RT-PCR in breast cancer and normal tissues. MiR-211 is significantly downregulated in breast cancer. MiR-211 re-expression suppressed cell growth, cell cycle, migration, and invasion in triple-negative breast cancer (TNBC) cell line MDA-MB231. Luciferase expression from a reporter vector containing the CDC25B -3'UTR was decreased when this construct was transfected with miR-211. The over-expression of miR-211 suppressed the endogenous CDC25B protein level in TNBC cells. For the first time, we demonstrate that miRNA-211 is a direct negative regulator of CDC25B expression in TNBC cells, alters other related target proteins CCNB1 and FOXM1, and then inhibits breast cancer cells growth, migration, and invasion and lead G2/M arrest. The transcriptional loss of miR-211 and the resultant increase in CDC25B expression facilitate increased genomic instability at an early stage of tumor development.