MicroRNA-138-5p inhibits cell migration, invasion and EMT in breast cancer by directly targeting RHBDD1.
BACKGROUND
Accumulating studies have identified that microRNAs (miRNAs) are novel regulators acting as tumor suppressors or oncogenes in tumor progression. The aim of the study is to investigate the functional roles of miR-138-5p in breast cancer (BC) cells and explore the underlying mechanisms by identifying its target gene.


METHODS AND RESULTS
Our results first showed that miR-138-5p expression was remarkably decreased in BC tissues and cells using quantitative real-time PCR analysis. Forced expression of miR-138-5p significantly suppressed cell migration and invasion ability of BC using transwell assay. Moreover, miR-138-5p overexpression suppressed cell epithelial-mesenchymal transition (EMT) phenomenon of BC by upregulating E-cadherin expression, but downregulating N-cadherin and Vimentin expression. More importantly, rhomboid domain-containing protein 1 (RHBDD1) was predicted as the direct target of miR-138-5p by TargetScan and miRanda, which was subsequently confirmed by luciferase reporter assay in BC cells. RHBDD1 was up-regulated in BC tissues and negatively correlated with miR-138-5p expression. Furthermore, forced expression of miR-138-5p could down-regulate the expression of RHBDD1, but overexpression of RHBDD1 reversed the suppressive effects of miR-138-5p in BC cell migration, invasion and EMT.


CONCLUSIONS
Our findings revealed the tumor-suppressive role of miR-138-5p in regulating BC migration by targeting RHBDD1, suggesting that miR-138-5p negatively regulating EMT might be a therapeutic target in BC.
['Zhao|Chengpeng|C|', 'Ling|Xiaoling|X|', 'Li|Xiangjin|X|', 'Hou|Xiaoming|X|', 'Zhao|Da|D|']
D015703:Antigens, CD D001943:Breast Neoplasms D015820:Cadherins D045744:Cell Line, Tumor D002465:Cell Movement D015536:Down-Regulation D058750:Epithelial-Mesenchymal Transition D005260:Female D015972:Gene Expression Regulation, Neoplastic D006801:Humans D035683:MicroRNAs D009361:Neoplasm Invasiveness D012697:Serine Endopeptidases D014162:Transfection D014746:Vimentin
Breast cancer RHBDD1 miR-138-5P Epithelial–mesenchymal transition