ABSTRACT
MicroRNA-142-3p (miR-142-3p) was previously investigated in various cancers, whereas, it's role in breast cancer (BC) remains far from understood. In this study, we found that miR-142-3p was markedly decreased both in cell lines and BC tumor tissues. Elevated miR-142-3p expression suppressed growth and metastasis of BC cell lines via gain-of-function assay in vitro and in vivo. Mechanistically, miR-142-3p could regulate the ras-related C3 botulinum toxin substrate 1 (RAC1) expression in protein level, which simultaneously suppressed the epithelial-to-mesenchymal transition related protein levels and the activity of PAK1 phosphorylation, respectively. In addition, rescue experiments revealed RAC1 overexpression could reverse tumor-suppressive role of miR-142-3p. Our results showed miR-142-3p could function as a tumor suppressor via targeting RAC1/PAK1 pathway in BC, suggesting a potent therapeutic target for BC treatment.
Subject(s)
Breast Neoplasms/enzymology , MicroRNAs/metabolism , p21-Activated Kinases/metabolism , rac1 GTP-Binding Protein/metabolism , Animals , Apoptosis , Breast Neoplasms/genetics , Breast Neoplasms/pathology , Cell Movement , Cell Proliferation , Databases, Genetic , Female , Gene Expression Regulation, Neoplastic , Humans , MCF-7 Cells , Mice, Inbred BALB C , Mice, Nude , MicroRNAs/genetics , Neoplasm Invasiveness , Neovascularization, Pathologic , Phosphorylation , Signal Transduction , p21-Activated Kinases/genetics , rac1 GTP-Binding Protein/geneticsABSTRACT
Colorectal cancer(CRC) is a prevalent malignancy in the world. There is growing evidence that microRNAs (miRNAs) as crucial modulator are in connection with many tumor-related diseases including CRC. Though miR-485-5p has been reported as an anti-oncogene in certain cancers, it remains unclear in CRC. In this research, we found that miR-485-5p was at lower level expression in CRC tissues and cell lines compared to the paired paracancerous tissues and the normal colon epithelial cell line FHC, correspondingly. Furthermore, Experimental up-regulation miR-485-5p in DLD-1 and SW480 cells with mimic could inhibit the ability of proliferation, migration, invasion of CRC cell lines and facilitate cells apoptosis. Also, we confirmed that CD147 existed typically negative regulation by miR-485-5p through binding a conserved sequence specifically within the CD147 3'-untranslated region (3'UTR) and reintroduction of CD147 could rescue the phenotypic changes caused by miR-485-5p. The findings provide evidence to demonstrate the role of miR-485-5p/CD147 interaction in CRC and indicate that miR-485-5p might be exploited therapeutically in CRC.