Department of Urology, Area 3, Tangshan Gongren Hospital, Tangshan City, Hebei Province, 063000, China.
Crit Rev Eukaryot Gene Expr. 2023;33(7):43-56. doi: 10.1615/CritRevEukaryotGeneExpr.2023048338.
The objective of this study was to determine the regulatory mechanism of MAGI2-AS3 in clear cell renal cell carcinoma (ccRCC), thereby supplying a new insight for ccRCC treatment. Expression data in TCGA-KIRC were obtained. Target gene lncRNA for research was determined using expression analysis and clinical analysis. lncRNA's downstream regulatory miRNA and mRNA were predicted by bioinformatics databases. ccRCC cell malignant phenotypes were detected via CCK-8, colony formation, Transwell migration, and invasion assays. The targeting relationship between genes was assessed through dual-luciferase reporter gene analysis. Kaplan-Meier (K-M) analysis was carried out to verify the effect of MAGI2-AS3, miR-629-5p, and PRDM16 on the survival rate of ccRCC patients. MAGI2-AS3 expression in ccRCC tissue and cells was shown to be markedly decreased and its expression to continuously decline with tumor progression. MAGI2-AS3 suppresses ccRCC proliferation and migration. Dual-luciferase assay showed that MAGI2-AS3 binds miR-629-5p and that miR-629-5p binds PRDM16. In addition, functional experiments showed that MAGI2-AS3 facilitates PRDM16 expression by repressing miR-629-5p expression, thereby suppressing ccRCC cell aggression. K-M analysis showed that upregulation of either MAGI2-AS3 or PRDM16 significantly improves ccRCC patient survival, while upregulation of miR-629-5p has no significant impact. MAGI2-AS3 sponges miR-629-5p to modulate PRDM16 to mediate ccRCC development. Meanwhile, the MAGI2-AS3/miR-629-5p/PRDM16 axis, as a regulatory pathway of ccRCC progression, may be a possible therapeutic target and prognostic indicator of ccRCC.
本研究旨在探讨 MAGI2-AS3 在肾透明细胞癌（ccRCC）中的调控机制，为 ccRCC 的治疗提供新的思路。从 TCGA-KIRC 中获取表达数据。通过表达分析和临床分析确定研究的靶基因 lncRNA。利用生物信息学数据库预测 lncRNA 的下游调控 miRNA 和 mRNA。通过 CCK-8、集落形成、Transwell 迁移和侵袭实验检测 ccRCC 细胞的恶性表型。通过双荧光素酶报告基因分析评估基因之间的靶向关系。通过 Kaplan-Meier（K-M）分析验证 MAGI2-AS3、miR-629-5p 和 PRDM16 对 ccRCC 患者生存率的影响。结果表明，MAGI2-AS3 在 ccRCC 组织和细胞中的表达明显降低，且其表达随肿瘤进展而持续下降。MAGI2-AS3 抑制 ccRCC 的增殖和迁移。双荧光素酶报告基因实验表明，MAGI2-AS3 与 miR-629-5p 结合，miR-629-5p 与 PRDM16 结合。此外，功能实验表明，MAGI2-AS3 通过抑制 miR-629-5p 的表达促进 PRDM16 的表达，从而抑制 ccRCC 细胞的侵袭。K-M 分析表明，上调 MAGI2-AS3 或 PRDM16 均可显著提高 ccRCC 患者的生存率，而上调 miR-629-5p 则无显著影响。MAGI2-AS3 作为 miR-629-5p 的海绵，调节 PRDM16 从而介导 ccRCC 的发生发展。同时，MAGI2-AS3/miR-629-5p/PRDM16 轴作为 ccRCC 进展的调控途径，可能是 ccRCC 治疗的潜在靶点和预后标志物。
