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长链非编码 RNA 115(LINC00115)通过靶向下调 6-磷酸果糖-2-激酶/果糖-2,6-二磷酸酶 2(PFKFB2)的 microRNA miR-489-3p 加重视网膜母细胞瘤的进展。

Long intergenic non-protein coding RNA 115 (LINC00115) aggravates retinoblastoma progression by targeting microRNA miR-489-3p that downregulates 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 2 (PFKFB2).

机构信息

Department of Ophthalmology, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, China.

出版信息

Bioengineered. 2022 Mar;13(3):5330-5343. doi: 10.1080/21655979.2022.2037362.

Abstract

Long non-coding RNAs (lncRNAs) are key regulators of cancer. However, the role of long intergenic non-protein coding RNA 115 (LINC00115) in the regulation of retinoblastoma (RB) has not yet been studied. The expression levels of LINC00115, microRNA (miR)-489-3p, and 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 2 (PFKFB2) in RB tissues or cells were detected by quantitative reverse transcription-polymerase chain reaction. The proliferation and migration of cells were detected by the cell counting kit-8 and Transwell assays. Luciferase reporter gene analysis and RNA immunoprecipitation assay were used to validate the target gene interactions predicted by starBase. A xenograft tumor experiment was conducted to validate the in vivo outcomes. The expression levels of LINC00115 and PFKFB2 in RB tissues were higher than those in normal tissues, while miR-489-3p showed the opposite trend. Silencing of LINC00115 inhibited the proliferation and migration of SO-RB50 and HXO-RB44 cells. An inhibitory or facilitated effect on RB tumorigenesis was observed following PFKFB2 silencing or miR-489-3p overexpression, respectively. Moreover, LINC00115 aggravated RB progression by targeting miR-489-3p, which downregulated PFKFB2. This finding improves our understanding of the relationship between LINC00115 and RB. Furthermore, miR-489-3p and PFKFB2 may be used as potential targets for RB prevention and treatment.

摘要

长链非编码 RNA(lncRNA)是癌症的关键调控因子。然而,长链非蛋白编码 RNA 115(LINC00115)在视网膜母细胞瘤(RB)调控中的作用尚未研究。通过定量逆转录-聚合酶链反应检测 RB 组织或细胞中 LINC00115、microRNA(miR)-489-3p 和 6-磷酸果糖-2-激酶/果糖-2,6-二磷酸酶 2(PFKFB2)的表达水平。通过细胞计数试剂盒-8 和 Transwell 分析检测细胞的增殖和迁移。利用 starBase 预测的靶基因相互作用进行荧光素酶报告基因分析和 RNA 免疫沉淀分析。进行异种移植肿瘤实验验证体内结果。与正常组织相比,RB 组织中 LINC00115 和 PFKFB2 的表达水平升高,而 miR-489-3p 则呈现相反的趋势。沉默 LINC00115 抑制 SO-RB50 和 HXO-RB44 细胞的增殖和迁移。沉默 PFKFB2 或过表达 miR-489-3p 分别观察到对 RB 肿瘤发生的抑制或促进作用。此外,LINC00115 通过靶向 miR-489-3p 加重 RB 进展,从而下调 PFKFB2。这一发现增进了我们对 LINC00115 与 RB 之间关系的理解。此外,miR-489-3p 和 PFKFB2 可能作为 RB 预防和治疗的潜在靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da66/8973781/314f651a7a48/KBIE_A_2037362_F0001_OC.jpg

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