Abdullah A Assiri1,2, Noha Mourad1,3, Minghai Shao1, Patrick Kiel4, Wanqing Liu5, Todd C Skaar4, Brian R Overholser6,4. 1. Department of Pharmacy Practice, College of Pharmacy, Purdue University, West Lafayette, IN, U.S.A. 2. Department of Clinical Pharmacy, King Khalid University, Abha, Kingdom of Saudi Arabia. 3. College of Pharmacy, Manchester University, Fort Wayne, IN, U.S.A. 4. Division of Clinical Pharmacology, Indiana University School of Medicine, Indianapolis, IN, U.S.A. 5. Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, MI, U.S.A. 6. Department of Pharmacy Practice, College of Pharmacy, Purdue University, West Lafayette, IN, U.S.A. boverhol@purdue.edu.
Abstract
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. Copyright
BACKGROUND/AIM: hERGpotassium 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. Copyright
Authors: H Kang; C Kim; H Lee; J G Rho; J-W Seo; J-W Nam; W K Song; S W Nam; W Kim; E K Lee Journal: Cell Death Differ Date: 2015-09-04 Impact factor: 15.828