In recent years, plenty of studies found that circular RNAs (circRNAs) were essential players in the initiation and progression of various cancers including the renal cell carcinoma (RCC). However, the knowledge about the circRNAs in carcinogenesis is still limited. Dysregulated expression of circNUP98 in RCC tissues was identified by the circular RNA microarray. RT‐PCR was performed to measure the expression of circNUP98 in 78 pairs of RCC tissues and adjacent normal tissues. Survival analysis was conducted to explore the association between the expression of circNUP98 and the prognosis of RCC. The function and underlying mechanisms of circSMC3 in RCC cells were investigated by RNAi, CCK‐8, Western blotting, bioinformatic analysis, ChIP assay, circRIP assay and dual luciferase reporter assay. CircNUP98 was up‐regulated in both RCC tissues and cell lines, and high expression of circNUP98 was correlated with poor prognosis of RCC patients. Silencing of circSMC3 inhibited the proliferation and promoted the apoptosis in a caspase‐dependent manner in RCC cells. Mechanistically, we revealed that silencing of circ NUP98 inhibited RCC progression by down‐regulating of PRDX3 via up‐regulation of miR‐567. Furthermore, STAT3 was identified as an inducer of circ NUP98 in RCC cells. CircNUP98 acts as an oncogene by a novel STAT3/circ NUP98/miR‐567/PRDX3 axis, which may provide a potential biomarker and therapeutic target for the treatment of RCC.

中文翻译：

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一种新型的circRNA，circNUP98，一种潜在的生物标志物，通过miR-567 / PRDX3轴在肾细胞癌中作为癌基因。

近年来，大量研究发现，环状RNA（circRNA）在包括肾细胞癌（RCC）在内的各种癌症的发生和发展中起着至关重要的作用。但是，关于circRNA在致癌性方面的知识仍然有限。通过环状RNA微阵列鉴定出RCC组织中circNUP98的表达失调。进行RT-PCR以测量circNUP98在78对RCC组织和邻近正常组织中的表达。进行生存分析以探讨circNUP98的表达与RCC预后的关系。通过RNAi，CCK-8，Western印迹，生物信息学分析，ChIP测定，circRIP测定和双重荧光素酶报告基因测定研究了circSMC3在RCC细胞中的功能和潜在机制。CircNUP98在RCC组织和细胞系中均上调，而circNUP98的高表达与RCC患者的预后不良相关。沉默circSMC3可抑制RCC细胞的增殖并促进caspase依赖性的凋亡。从机制上讲，我们揭示了circ NUP98沉默通过上调miR-567来下调PRDX3，从而抑制了RCC进程。此外，STAT3被鉴定为RCC细胞中circ NUP98的诱导剂。CircNUP98通过新型STAT3 / circ NUP98 / miR-567 / PRDX3轴作为癌基因，可能为RCC的治疗提供潜在的生物标志物和治疗靶标。沉默circSMC3可抑制RCC细胞的增殖，并以caspase依赖性方式促进其凋亡。从机制上讲，我们揭示了circ NUP98的沉默通过上调miR-567下调PRDX3而抑制了RCC进程。此外，STAT3被鉴定为RCC细胞中circ NUP98的诱导剂。CircNUP98通过新型STAT3 / circ NUP98 / miR-567 / PRDX3轴作为癌基因，可能为RCC的治疗提供潜在的生物标志物和治疗靶标。沉默circSMC3可抑制RCC细胞的增殖，并以caspase依赖性方式促进其凋亡。从机制上讲，我们揭示了circ NUP98的沉默通过上调miR-567下调PRDX3而抑制了RCC进程。此外，STAT3被鉴定为RCC细胞中circ NUP98的诱导剂。CircNUP98通过新型STAT3 / circ NUP98 / miR-567 / PRDX3轴作为癌基因，可能为RCC的治疗提供潜在的生物标志物和治疗靶标。