Department of Ophthalmology, The Affiliated Xuzhou Municipal Hospital of Xuzhou Medical University, Xuzhou, China.
Department of Ophthalmology, The Affiliated Hospital of China University of Mining and Technology, Xuzhou Eye Research Institute, Xuzhou, Jiangsu, China.
Curr Eye Res. 2021 Jul;46(7):978-987. doi: 10.1080/02713683.2020.1843685. Epub 2021 May 7.
: Retinoblastoma (RB) is a frequent intraocular malignancy in children. Circular RNA (circRNA) plays an essential role in regulating the occurrence and development of tumors. This study aimed at investigating the function and molecular basis of hsa_circ_0093996 (circTET1) in RB.: The expression of circTET1, miR-492 and miR-494-3p was examined using quantitative real-time polymerase chain reaction. Cell proliferation, cycle arrest, apoptosis, migration and invasion of RB cells were detected using Cell Counting Kit-8 (CCK-8), colony formation assay, flow cytometry, scratch assay and transwell analysis, respectively. The levels of matrix metalloproteinase (MMP) 2, MMP9 and Wnt/β-catenin pathway-related proteins were measured via western blot assay. The association between circTET1 and miR-492/miR-494-3p was validated via dual-luciferase reporter assay and RNA pull-down assay. Xenograft assay was employed to analyze tumor growth .: CircTET1 level was reduced, while miR-492 and miR-494-3p levels were increased in RB tissues and cells. Overexpression of circTET1 inhibited proliferation, migration and invasion, and promoted apoptosis and cell cycle arrest in Y79 and WERI-Rb1 cells. Moreover, circTET1 impeded RB cell progression by sponging miR-492/miR-494-3p. Also, up-regulation of circTET1 restrained Wnt/β-catenin pathway via regulating miR-492 and miR-494-3p. Furthermore, circTET1 suppressed tumor growth in xenograft models.: CircTET1 inhibited RB progression by sponging miR-492/miR-494-3p and inactivating the Wnt/β-catenin pathway, which provided new insights for RB treatment.
视网膜母细胞瘤（RB）是儿童常见的眼内恶性肿瘤。环状 RNA（circRNA）在肿瘤的发生和发展中起着重要作用。本研究旨在探讨 hsa_circ_0093996（circTET1）在 RB 中的功能和分子基础。
采用实时定量聚合酶链反应检测 circTET1、miR-492 和 miR-494-3p 的表达。采用细胞计数试剂盒-8（CCK-8）检测 RB 细胞的增殖、周期阻滞、凋亡、迁移和侵袭，分别采用集落形成实验、流式细胞术、划痕实验和 Transwell 分析检测。采用 Western blot 检测基质金属蛋白酶（MMP）2、MMP9 和 Wnt/β-catenin 通路相关蛋白的水平。通过双荧光素酶报告基因检测和 RNA 下拉实验验证 circTET1 与 miR-492/miR-494-3p 的相关性。采用异种移植实验分析肿瘤生长情况。
结果显示，RB 组织和细胞中 circTET1 水平降低，miR-492 和 miR-494-3p 水平升高。在 Y79 和 WERI-Rb1 细胞中，过表达 circTET1 抑制增殖、迁移和侵袭，促进细胞凋亡和细胞周期阻滞。此外，circTET1 通过海绵吸附 miR-492/miR-494-3p 抑制 RB 细胞进展。此外，上调 circTET1 通过调节 miR-492 和 miR-494-3p 抑制 Wnt/β-catenin 通路。此外，circTET1 抑制异种移植模型中的肿瘤生长。
综上所述，circTET1 通过海绵吸附 miR-492/miR-494-3p 并使 Wnt/β-catenin 通路失活，抑制 RB 进展，为 RB 治疗提供了新的思路。
