Department of Ophthalmology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Department of Ophthalmology, Shanghai Eighth People Hospital, Shanghai, China
Bioengineered. 2022 Mar;13(3):7410-7424. doi: 10.1080/21655979.2022.2048770.
Retinoblastoma, often referred to as eye cancer, is a common primary pediatric intraocular malignancy. In this framework, micro ribose nucleic acids (miRNAs) play essential roles in retinoblastoma oncogenesis and development. However, the function and mechanism of the miR-141-3p/sushi domain-containing protein 2 (SUSD2) axis in retinoblastoma are unclear. To address these issues, miR-141-3p and SUSD2 expressions between the retinoblastoma patients and the normal control are identified by analyzing the Gene Expression Omnibus (GEO) datasets. Moreover, bioinformatics analysis, a dual-luciferase reporter assay, functional loss, and gain together with rescue experiments are employed to explore the biological function and molecular mechanisms of the miR-141-3p/SUSD2 axis in retinoblastoma oncogenesis and development. Our data showed that SUSD2 levels are considerably decreased in retinoblastoma cells and tissues. SUSD2 overexpression inhibited viability, promoting apoptosis of retinoblastoma cells and inhibiting tube formation of primary human umbilical vein endothelial cells (HUVECs) . The bioinformatics analysis and dual-luciferase reporter tests showed that SUSD2 is directly regulated by miR-141-3p. The miR-141-3p inhibition suppressed retinoblastoma growth and angiogenesis, while miR-141-3p overexpression increased retinoblastoma growth and angiogenesis, which is partially reversed when SUSD2 is over-expressed both and . In conclusion, SUSD2 is a tumor-suppressor in retinoblastoma. miR-141-3p/SUSD2 axis played an essential role in regulating angiogenesis and retinoblastoma progression, serving as a new biomarker for management of retinoblastoma.
视网膜母细胞瘤,通常被称为眼癌,是一种常见的小儿眼内原发性恶性肿瘤。在这个框架中,微小核糖核酸(miRNAs)在视网膜母细胞瘤的发生和发展中起着重要作用。然而,miR-141-3p/含 sushi 结构域蛋白 2(SUSD2)轴在视网膜母细胞瘤中的功能和机制尚不清楚。为了解决这些问题,通过分析基因表达综合数据库(GEO)数据集,确定了视网膜母细胞瘤患者和正常对照组之间 miR-141-3p 和 SUSD2 的表达。此外,还采用生物信息学分析、双荧光素酶报告基因检测、功能丧失和获得以及挽救实验,探讨了 miR-141-3p/SUSD2 轴在视网膜母细胞瘤发生和发展中的生物学功能和分子机制。我们的数据表明,SUSD2 在视网膜母细胞瘤细胞和组织中的水平明显降低。SUSD2 过表达抑制了视网膜母细胞瘤细胞的活力,促进了其凋亡,并抑制了原代人脐静脉内皮细胞(HUVEC)的管形成。生物信息学分析和双荧光素酶报告基因检测表明,SUSD2 可被 miR-141-3p 直接调控。抑制 miR-141-3p 可抑制视网膜母细胞瘤的生长和血管生成,而过表达 miR-141-3p 则增加了视网膜母细胞瘤的生长和血管生成,当 SUSD2 过表达时,这种情况部分得到了逆转。总之,SUSD2 是视网膜母细胞瘤的肿瘤抑制因子。miR-141-3p/SUSD2 轴在调节血管生成和视网膜母细胞瘤进展中起着重要作用,可作为管理视网膜母细胞瘤的新生物标志物。