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miR-338-3p/NOVA1 轴在视网膜母细胞瘤中的作用。

Roles of the microRNA‑338‑3p/NOVA1 axis in retinoblastoma.

机构信息

Department of Ophthalmology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China.

Department of Ophthalmology, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China.

出版信息

Mol Med Rep. 2021 May;23(5). doi: 10.3892/mmr.2021.12033. Epub 2021 Mar 24.

Abstract

Retinoblastoma (RB) is an intraocular malignancy that mainly affects young children. Previous reports have demonstrated that mutations or the inactivation of the RB1 gene were the main cause of RB; however, disruption of the intracellular signaling pathways following deficiency of RB1 requires further investigation. Based on the Gene Expression Omnibus data and bioinformatics prediction, the present study aimed to investigate the microRNA (miR)‑338‑3p/neuro‑oncological ventral antigen 1 (NOVA1) axis in RB. Subsequently, overexpression and knockdown of miR‑338‑3p and NOVA1, respectively, were performed to study the role of miR‑338‑3p/NOVA1 in the progression of the RB cells. The results demonstrated that overexpression of miR‑338‑3p significantly inhibited cell proliferation, migration and invasion, and promoted apoptosis of the RB cells. Moreover, knockdown of NOVA1 showed similar results. A dual‑luciferase reporter assay and rescue experiments further confirmed the direct binding between miR‑338‑3p and NOVA1. Taken together, the results indicated that miR‑338‑3p acted as tumor suppressor by targeting the oncogene of NOVA1 in RB, which may serve as potential therapeutic targets in RB.

摘要

视网膜母细胞瘤(RB)是一种主要影响儿童的眼内恶性肿瘤。先前的报告表明,RB1 基因的突变或失活是 RB 的主要原因;然而,RB1 缺乏后细胞内信号通路的中断需要进一步研究。基于基因表达综合数据库和生物信息学预测,本研究旨在探讨 RB 中的 microRNA(miR)-338-3p/神经肿瘤性腹侧抗原 1(NOVA1)轴。随后,分别过表达和敲低 miR-338-3p 和 NOVA1,以研究 miR-338-3p/NOVA1 在 RB 细胞进展中的作用。结果表明,过表达 miR-338-3p 可显著抑制 RB 细胞的增殖、迁移和侵袭,并促进其凋亡。此外,敲低 NOVA1 也得到了类似的结果。双荧光素酶报告基因检测和挽救实验进一步证实了 miR-338-3p 和 NOVA1 之间的直接结合。综上所述,这些结果表明,miR-338-3p 通过靶向 RB 中的癌基因 NOVA1 发挥肿瘤抑制作用,这可能成为 RB 的潜在治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fdda/8008220/450363af72b1/mmr-23-05-12033-g00.jpg

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