Circular RNA circ‐EGLN3 promotes renal cell carcinoma proliferation and aggressiveness via miR‐1299‐mediated IRF7 activation

Abstract 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.