微小 RNA 362-3p 减少 hERG 相关电流并抑制乳腺癌细胞增殖。
MicroRNA 362-3p Reduces hERG-related Current and Inhibits Breast Cancer Cells Proliferation.
机构信息
Department of Pharmacy Practice, College of Pharmacy, Purdue University, West Lafayette, IN, U.S.A.
Department of Clinical Pharmacy, King Khalid University, Abha, Kingdom of Saudi Arabia.
出版信息
Cancer Genomics Proteomics. 2019 Nov-Dec;16(6):433-442. doi: 10.21873/cgp.20147.
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.
背景/目的：hERG 钾通道增强肿瘤侵袭性和乳腺癌增殖。癌症期间 microRNA（miRNA）的失调控制基因调控。本研究的目的是确定调节乳腺癌中 hERG 表达的 miRNA。
材料和方法
通过生物信息学方法鉴定靶向 hERG 的假定 miRNA，并通过 3'UTR 荧光素酶测定进行筛选。miRNA、hERG siRNA 或对照转染后，通过全细胞电生理学、增殖测定和细胞周期分析对内源性 hERG 调节进行功能评估。
结果
miR-362-3p 靶向 hERG 3'UTR，与乳腺癌患者的生存率较高相关（HR=0.39，95%CI=0.18-0.82）。增强的 miR-362-3p 表达降低了培养的乳腺癌细胞中的 hERG 表达、峰值电流和细胞增殖（p<0.05）。
结论
miR-362-3p 介导 hERG 的转录调节，并与乳腺癌的生存相关。miR-362-3p 作为生物标志物并为治疗策略提供信息的潜力值得进一步研究。
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