Background

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.

Methods

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.

Results

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.

Conclusion

Circ-EGLN3 regulated RCC progression through the miR-1224-3p/HMGXB3 axis, suggesting its potential as a therapeutic target.

中文翻译：

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环状 RNA EGLN3 沉默通过 miR-1224-3p/HMGXB3 轴抑制肾细胞癌进展

背景

肾细胞癌（RCC）是泌尿系统常见的肿瘤，其全球发病率呈逐年上升趋势。环状 RNA (circRNA) 参与 RCC 肿瘤发生；然而，源自 Egl 9 同源物 3 (EGLN3) 基因的 circ-EGLN3 (hsa_circ_0031594) 在 RCC 中的作用仍未确定。

方法

在 RCC 细胞和组织中，在 RNase R 和放线菌素处理之前和之后检查了 Circ-EGNL3 的表达。使用 CCK-8 测定、EdU 染色、伤口愈合和 Transwell 测定评估细胞增殖、迁移和侵袭。通过生物信息学分析预测 microRNA (miR)-1224-3p 与 circ-EGLN3 之间以及 miR-1224-3p 与 HMG box domain containing 3 (HMGXB3) 之间的相互作用，并通过双荧光素酶报告基因分析进行验证。

结果

使用 RNase R 和放线菌素处理鉴定了 Circ-EGLN3。Circ-EGLN3 在 RCC 细胞和组织中上调，并与较差的总体存活率相关。circ-EGNL3 的沉默降低了 RCC 细胞的增殖、迁移和侵袭。机制研究表明，circ-EGNL3 充当了靶向 HMGXB3 的 miR-1224-3p 的海绵。Circ-EGNL3 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 RCC 的抑制作用。

结论

Circ-EGLN3 通过 miR-1224-3p/HMGXB3 轴调节 RCC 进展，表明其作为治疗靶点的潜力。