Zhang Gang, Wang Jianqiang, Tan Wei, Han Xiang, Han Baoshuai, Wang Hao, Xia Yong, Sun Yi, Li Hang
Department of Urinary Surgery, Hanzhong People's Hospital, Hanzhong, Shaanxi, 723000, China.
Department of Urinary Surgery, Hanzhong Central Hospital, Hanzhong, Shaanxi, 723000, China.
Acta Histochem. 2021 Sep;123(6):151752. doi: 10.1016/j.acthis.2021.151752. Epub 2021 Jul 15.
Renal cell carcinoma (RCC) is a common tumor of the urinary system, and its global incidence is increasing annually. Circular RNAs (circRNAs) are involved in RCC tumorigenesis; however, the role of circ-EGLN3 (hsa_circ_0031594) derived from the Egl nine homolog 3 (EGLN3) gene in RCC remains undetermined.
Circ-EGNL3 expression was examined before and after RNase R and actinomycin treatments in RCC cells and tissues. Cell proliferation, migration, and invasion were assessed using the CCK-8 assay, EdU staining, and wound-healing and Transwell assays. The interactions between microRNA (miR)-1224-3p and circ-EGLN3, and between miR-1224-3p and HMG box domain containing 3 (HMGXB3) were predicted by bioinformatics analysis and validated by dual-luciferase reporter assay.
Circ-EGLN3 was identified using RNase R and actinomycin treatments. Circ-EGLN3 was upregulated in RCC cells and tissues and correlated with poor overall survival. Silencing of circ-EGNL3 decreased RCC cell proliferation, migration, and invasion. Mechanistic studies indicated that circ-EGNL3 acts as a sponge for miR-1224-3p, which targeted HMGXB3. Circ-EGNL3 indirectly upregulated HMGXB3 by targeting miR-1224-3p, and overexpression of circ-EGLN3 reversed the repressive effects of miR-1224-3p on RCC.
Circ-EGLN3 regulated RCC progression through the miR-1224-3p/HMGXB3 axis, suggesting its potential as a therapeutic target.
肾细胞癌（RCC）是泌尿系统的常见肿瘤，其全球发病率逐年上升。环状RNA（circRNAs）参与肾细胞癌的肿瘤发生；然而，源自Egl九同源物3（EGLN3）基因的circ-EGLN3（hsa_circ_0031594）在肾细胞癌中的作用仍未确定。
在肾癌细胞和组织中，用核糖核酸酶R和放线菌素处理前后检测circ-EGNL3的表达。使用CCK-8试验、EdU染色、伤口愈合试验和Transwell试验评估细胞增殖、迁移和侵袭。通过生物信息学分析预测微小RNA（miR）-1224-3p与circ-EGLN3之间以及miR-1224-3p与含HMG盒结构域3（HMGXB3）之间的相互作用，并通过双荧光素酶报告基因试验进行验证。
通过核糖核酸酶R和放线菌素处理鉴定出circ-EGLN3。circ-EGLN3在肾癌细胞和组织中上调，与总体生存率差相关。circ-EGNL3沉默降低了肾癌细胞的增殖、迁移和侵袭。机制研究表明，circ-EGLN3作为miR-1224-3p的海绵，后者靶向HMGXB3。circ-EGLN3通过靶向miR-1224-3p间接上调HMGXB3，circ-EGLN3的过表达逆转了miR-1224-3p对肾细胞癌的抑制作用。
circ-EGLN3通过miR-1224-3p/HMGXB3轴调节肾细胞癌进展，提示其作为治疗靶点的潜力。
