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miR-146a 通过负向调控神经母细胞瘤性脑肿瘤抗原-1 发挥抑癌作用,抑制视网膜母细胞瘤的发生。

MiR-146a functions as a potential tumor suppressor in retinoblastoma by negatively regulate neuro-oncological ventral antigen-1.

机构信息

Department of Ophthalmology, The Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University, Huai 'an City, Jiangsu, China.

出版信息

Kaohsiung J Med Sci. 2021 Apr;37(4):286-293. doi: 10.1002/kjm2.12337. Epub 2020 Dec 19.

Abstract

MicroRNAs (miRNAs) are dysregulated in many tumors and have been found to play crucial roles in cancer biology. Retinoblastoma is a rare tumor that develops rapidly from a malignant tumor of immature cells in the retina known as photoreceptor progenitors. Our study aimed to explore the role of miR-146a in the pathology of retinoblastoma. Potential target gene of miR-146a was predicted by Targetscan. Reverse transcription quantitative polymerase chain reaction (RT-PCR) showed that miR-146a was downregulated and ventral nerve tumor antigen 1 (Neuro - oncological ventral antigen 1, NOVA1) was upregulated in retinoblastoma. Luciferase assay confirmed that miR-146a directly target NOVA1. MiR-146a knockdown and overexpression experiments were performed and found that miR-146a could regulate the expression of NOVA1. The miR-146a knockdown and overexpression experiments were conducted to investigate the biological function of miR-146a. MiR-146a was found inhibited the viability, proliferation and invasion of retinoblastoma cell by MTT, EdU, and transwell assays. Flow cytometry was performed for the apoptosis analysis and miR-146a increased the apoptosis of retinoblastoma cell was found. Above phenomenon can be rescued by overexpression of NOVA1. In conclusion, these results suggest that miR-146a acts as a tumor suppressor and can act as a potential therapeutic target for retinoblastoma in the future.

摘要

微小 RNA(miRNAs)在许多肿瘤中失调,并被发现在癌症生物学中发挥关键作用。视网膜母细胞瘤是一种罕见的肿瘤,它是由视网膜中未成熟细胞的恶性肿瘤(称为光感受器祖细胞)迅速发展而来的。我们的研究旨在探索 miR-146a 在视网膜母细胞瘤发病机制中的作用。通过 Targetscan 预测 miR-146a 的潜在靶基因。逆转录定量聚合酶链反应(RT-PCR)显示,miR-146a 在视网膜母细胞瘤中下调,而腹神经肿瘤抗原 1(神经肿瘤腹抗原 1,NOVA1)上调。荧光素酶报告基因实验证实 miR-146a 可直接靶向 NOVA1。进行了 miR-146a 敲低和过表达实验,发现 miR-146a 可以调节 NOVA1 的表达。进行了 miR-146a 敲低和过表达实验,以研究 miR-146a 的生物学功能。通过 MTT、EdU 和 Transwell 测定发现 miR-146a 抑制视网膜母细胞瘤细胞的活力、增殖和侵袭。通过流式细胞术进行凋亡分析发现 miR-146a 增加了视网膜母细胞瘤细胞的凋亡。上述现象可通过 NOVA1 的过表达得到挽救。总之,这些结果表明 miR-146a 作为一种肿瘤抑制因子,将来可能成为治疗视网膜母细胞瘤的潜在靶点。

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