Abstract P2-03-08: miR-621 suppresses the metastatic cascade in breast cancer patients

Abstract

Abstract Purpose: In previous study, we had shown that miR-621 could sensitize breast cancer to chemotherapy by suppressing FBXO11 and enhancing p53 activity. In this study, we aimed to define miR-621 prognosis value in breast cancer patients, and to explore the potential molecular mechanisms. Experimental Design: 70 patients with stages II and III breast cancer were included as validation set. The correlation between miR-621 expression level and prognosis in breast cancer patients was confirmed. In parallel, in vitro and in vivo analyses were carried out to determine the potential mechanisms of miRNA-dependent prognosis. Results: We validated that lower than higher miR-621 expression level was markedly associated with poor metastasis-free survival in breast cancer patients(P=0.03). In breast cancer cell lines, ectopic overexpression of miR-621 inhibited proliferation, migration, invasion, and metastasis both in vitro and in vivo. The potential miR-621-target genes were determined by TargetScan and miRNA CLIP-seq database. Among those, PAK7 was verified as one of the direct targets of miR-621 in breast cancer cells, whose expression level positively associated with recurrence and metastasis in breast cancer patients. The molecular mechanisms by which miR-621/PAK7 axis regulates recurrence and metastasis may involve regulation of epithelial-mesenchymal transition (EMT) in breast cancer cells. Conclusions: Our study revealed a strong correlation between miR-621 expression and metastasis in breast cancers. High level of miR-621 was negatively associated with poor metastasis-free survival. The increased metastasis-free survival may be mediated by down-regulation of PAK7 gene, which leads to reduced EMT in breast cancer cells. Therefore, miR-621 may represent a therapeutic target for early metastasis breast cancer. Citation Format: Xue J, Chi Y, Chen J, Yang B, Wu J. miR-621 suppresses the metastatic cascade in breast cancer patients. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P2-03-08.