miR-515-5p对视网膜母细胞瘤细胞增殖及药物敏感性的影响
Effect of miR-515-5p on Proliferation and Drug Sensitivity of Retinoblastoma Cells.
作者信息
Yuan Xiang Wen, Yan Ting Qin, Tong Huilin
机构信息
Department of Ophthalmology, Jinan People's Hospital, Jinan City, Shandong Province 271199, People's Republic of China.
Department of Ophthalmology, Tai'an Central Hospital, Tai'an City, Shandong Province 271000, People's Republic of China.
出版信息
Cancer Manag Res. 2020 Nov 24;12:12087-12098. doi: 10.2147/CMAR.S271165. eCollection 2020.
BACKGROUND
Retinoblastoma (RB) is a common malignancy in children eyes. Aberrant microRNA (miR) expression is observed in many cancer cases. miR-515-5p is reported to be concerned with the course of many cancers. This study explores the role of miR-515-5p in proliferation and drug sensitivity of RB cells.
METHODS
Human RB cell lines (WERI-RB1, SO-RB50 and Y79) and human retinal pigment epithelial cell line ARPE-19 were utilized in this study. Drug-resistant cells SO-RB50/VCR and SO-RB50/CBP were constructed for the following experiments. The expressions of miR-515-5p and Notch1 in RB cells were detected. Notch1 was significantly upregulated in RB cells while miR-515-5p was notably downregulated. Then, the binding relationship between miR-515-5p and Notch1 was predicted and verified.
RESULTS
miR-515-5p negatively regulated Notch1 expression. In vitro and in vivo experiments revealed that overexpressed miR-515-5p inhibited RB cell proliferation and enhanced drug sensitivity. Functional rescue experiment suggested that miR-515-5p regulated RB cell proliferation and drug sensitivity via inhibiting Notch1 expression.
CONCLUSION
It could be concluded that overexpressed miR-515-5p suppressed proliferation and drug resistance of RB cells by targeting Notch1 expression, indicating that miR-515-5p might constitute a promising therapy target for RB.
背景
视网膜母细胞瘤(RB)是儿童眼部常见的恶性肿瘤。在许多癌症病例中都观察到了异常的微小RNA(miR)表达。据报道,miR-515-5p与多种癌症的病程有关。本研究探讨miR-515-5p在RB细胞增殖和药物敏感性中的作用。
方法
本研究使用了人RB细胞系(WERI-RB1、SO-RB50和Y79)以及人视网膜色素上皮细胞系ARPE-19。构建了耐药细胞系SO-RB50/VCR和SO-RB50/CBP用于后续实验。检测了RB细胞中miR-515-5p和Notch1的表达。RB细胞中Notch1显著上调,而miR-515-5p明显下调。然后,预测并验证了miR-515-5p与Notch1之间的结合关系。
结果
miR-515-5p负向调节Notch1的表达。体外和体内实验表明,过表达miR-515-5p可抑制RB细胞增殖并增强药物敏感性。功能挽救实验表明,miR-515-5p通过抑制Notch1表达来调节RB细胞增殖和药物敏感性。
结论
可以得出结论,过表达的miR-515-5p通过靶向Notch1表达抑制RB细胞的增殖和耐药性,表明miR-515-5p可能成为RB的一个有前景的治疗靶点。