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长链非编码 RNA LINC00205 通过作为 microRNA-665 的分子海绵,从而增加 HMGB1 表达,增强视网膜母细胞瘤的恶性特征。

Long noncoding RNA LINC00205 enhances the malignant characteristics of retinoblastoma by acting as a molecular sponge of microRNA-665 and consequently increasing HMGB1 expression.

机构信息

Department of Ophthalmology, The First People's Hospital of Jinzhou (Yangtze University Affiliated First People's Hospital), Hubei, 434000, PR China.

Department of Oncology, Jingzhou Central Hospital, The Second Clinical Medical College of Yangtze University, Hubei, 434020, PR China.

出版信息

Biochem Biophys Res Commun. 2020 May 28;526(2):396-403. doi: 10.1016/j.bbrc.2020.03.083. Epub 2020 Mar 26.

DOI:10.1016/j.bbrc.2020.03.083
PMID:32223925
Abstract

Long intergenic non-protein-coding RNA 00205 (LINC00205) has been found to play crucial roles in hepatocellular carcinoma progression. In this study, we aimed to determine the expression pattern of LINC00205 in retinoblastoma (RB), to identify its functions in RB progression in detail, and to reveal the underlying mechanisms. Herein, we showed that LINC00205 is highly expressed in RB tissues and cell lines. The LINC00205 upregulation correlated with adverse clinicopathological parameters and shorter overall survival in patients with RB. LINC00205 depletion decreased the proliferative, migratory, and invasive abilities; promoted the apoptosis of RB cells in vitro; and impeded the tumor growth of RB cells in vivo. Mechanism investigation revealed that LINC00205 can act as a competing endogenous RNA by sponging microRNA-665 (miR-665) in RB cells, thereby upregulating miR-665's target: high-mobility group box 1 (HMGB1). Finally, rescue experiments confirmed that enhancing the miR-665-HMGB1 axis output attenuated the influence of the LINC00205 knockdown on RB cells. To sum up, the newly identified LINC00205-miR-665-HMGB1 pathway was systematically studied and may be validated as a potential target for RB diagnosis, prognosis, and therapy.

摘要

长链非编码 RNA 00205(LINC00205)已被发现在肝细胞癌的进展中发挥关键作用。在这项研究中,我们旨在确定 LINC00205 在视网膜母细胞瘤(RB)中的表达模式,详细确定其在 RB 进展中的功能,并揭示潜在的机制。在此,我们表明 LINC00205 在 RB 组织和细胞系中高度表达。LINC00205 的上调与 RB 患者的不良临床病理参数和总生存期缩短相关。LINC00205 的耗竭降低了 RB 细胞的增殖、迁移和侵袭能力;促进了 RB 细胞的体外凋亡;并阻碍了 RB 细胞的体内肿瘤生长。机制研究表明,LINC00205 可以作为 RB 细胞中的竞争性内源性 RNA,通过海绵吸附 microRNA-665(miR-665),从而上调 miR-665 的靶标:高迁移率族蛋白 1(HMGB1)。最后,挽救实验证实,增强 miR-665-HMGB1 轴的输出减弱了 LINC00205 敲低对 RB 细胞的影响。总之,系统研究了新发现的 LINC00205-miR-665-HMGB1 通路,可能被验证为 RB 诊断、预后和治疗的潜在靶点。

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