MicroRNA 362-3p Reduces hERG-related Current and Inhibits Breast Cancer Cells Proliferation
2019
BACKGROUND/AIM: hERG potassium channels enhance tumor invasiveness and breast cancer proliferation. MicroRNA (miRNA) dysregulation during cancer controls gene regulation. The objective of this study was to identify miRNAs that regulate hERG expression in breast cancer. MATERIALS AND METHODS: Putative miRNAs targeting hERG were identified by bioinformatic approaches and screened using a 3'UTR luciferase assay. Functional assessments of endogenous hERG regulation were made using whole-cell electrophysiology, proliferation assays, and cell-cycle analyses following miRNA, hERG siRNA, or control transfection. RESULTS: miR-362-3p targeted hERG 3'UTR and was associated with higher survival rates in patients with breast cancer (HR=0.39, 95%CI=0.18-0.82). Enhanced miR-362-3p expression reduced hERG expression, peak current, and cell proliferation in cultured breast cancer cells (p<0.05). CONCLUSION: miR-362-3p mediates the transcriptional regulation of hERG and is associated with survival in breast cancer. The potential for miR-362-3p to serve as a biomarker and inform therapeutic strategies warrants further investigation.
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