Department of Nephrology, The Third Affiliated Hospital of Qiqihar Medical University, Qiqihar, China.
Department of Blood Transfusion, The Third Affiliated Hospital of Qiqihar Medical University, Qiqihar, China.
J Cell Biochem. 2020 Nov;121(11):4377-4385. doi: 10.1002/jcb.29620. Epub 2020 Jan 6.
Renal cell carcinoma (RCC) is a highly lethal cancer with increasing incidence worldwide. The purpose of the present study was to investigate the functions and molecular mechanisms of circular RNA (circRNA), circ-EGLN3, in RCC progression. The expression levels of circ-EGLN3 were assessed by a quantitative real-time polymerase chain reaction. Kaplan-Meier analysis was applied to uncover the prognostic role of circ-EGLN3 in patients with RCC. Cell viability was analyzed using cell counting kit-8 and cell apoptosis was assessed using flow cytometric experiment. Cell migratory and invasive abilities were determined by wound scratch and transwell experiments. Subcellular distribution detection was utilized to investigate the location of circ-EGLN3. Dual-luciferase reporter test was utilized for identifying the molecular mechanism of circ-EGLN3. The results indicated that circ-EGLN3 was elevated in RCC tissues and cell lines and predicted unfavorable prognosis for the patients with RCC. Silenced circ-EGLN3 hindered cell proliferation, migration, and invasion but facilitated apoptosis of RCC cells. Ectopic expressed circ-EGLN3 induced the opposite effects mentioned above. Mechanistically, circ-EGLN3 was mainly located at the cytoplasm. Circ-EGLN3 acted as a competing endogenous RNA (ceRNA) to enhance the IRF7 level via sponging miR-1299. Moreover, circ-EGLN3 mediated elevation of IRF7 is responsible for RCC cell proliferation and aggressiveness. Collectively, our study suggested that circ-EGLN3 knockdown suppressed RCC progression through acting as a ceRNA to regulate the IRF7 expression by targeting miR-1299. Circ-EGLN3 might be a potential therapeutic target for RCC management.
肾细胞癌（RCC）是一种具有全球发病率不断增加的高致死性癌症。本研究旨在探讨环状 RNA（circRNA）circ-EGLN3 在 RCC 进展中的作用和分子机制。通过实时定量聚合酶链反应评估 circ-EGLN3 的表达水平。应用 Kaplan-Meier 分析揭示 circ-EGLN3 在 RCC 患者中的预后作用。使用细胞计数试剂盒-8 分析细胞活力，通过流式细胞术实验评估细胞凋亡。通过划痕实验和 Transwell 实验测定细胞迁移和侵袭能力。利用亚细胞分布检测来研究 circ-EGLN3 的位置。利用双荧光素酶报告实验鉴定 circ-EGLN3 的分子机制。结果表明，circ-EGLN3 在 RCC 组织和细胞系中升高，并预测 RCC 患者的预后不良。沉默 circ-EGLN3 抑制 RCC 细胞的增殖、迁移和侵袭，但促进细胞凋亡。外源性表达 circ-EGLN3 则诱导了上述相反的作用。机制上，circ-EGLN3 主要位于细胞质中。circ-EGLN3 作为竞争性内源性 RNA（ceRNA），通过海绵吸附 miR-1299 来增强 IRF7 水平。此外，circ-EGLN3 介导的 IRF7 升高是 RCC 细胞增殖和侵袭性的原因。总之，我们的研究表明，circ-EGLN3 敲低通过作为 ceRNA 通过靶向 miR-1299 来调节 IRF7 表达来抑制 RCC 进展。circ-EGLN3 可能是 RCC 管理的潜在治疗靶点。
