一种新的环状 RNA，环状 NUP98，一种潜在的生物标志物，通过 miR-567/PRDX3 轴在肾细胞癌中发挥癌基因作用。
A novel circRNA, circNUP98, a potential biomarker, acted as an oncogene via the miR-567/ PRDX3 axis in renal cell carcinoma.
机构信息
Zhejiang Key Laboratory of Pathophysiology, Department of Biochemistry and Molecular Biology, Medical School, Ningbo University, Ningbo, China.
School of Marine Science, Ningbo University, Ningbo, China.
出版信息
J Cell Mol Med. 2020 Sep;24(17):10177-10188. doi: 10.1111/jcmm.15629. Epub 2020 Jul 30.
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.
近年来，大量研究发现环状 RNA（circRNAs）是包括肾细胞癌（RCC）在内的多种癌症发生和发展的重要参与者。然而，关于 circRNAs 在致癌作用中的知识仍然有限。通过环状 RNA 微阵列鉴定了 RCC 组织中 circNUP98 的失调表达。通过 RT-PCR 测量了 78 对 RCC 组织和相邻正常组织中 circNUP98 的表达。进行生存分析以探讨 circNUP98 的表达与 RCC 预后之间的关系。通过 RNAi、CCK-8、Western blot、生物信息学分析、ChIP 测定、circRIP 测定和双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，circNUP98 的高表达与 RCC 患者的预后不良相关。circSMC3 的沉默以依赖半胱天冬酶的方式抑制 RCC 细胞的增殖并促进细胞凋亡。在机制上，我们揭示了沉默 circNUP98 通过上调 miR-567 下调 PRDX3 来抑制 RCC 进展。此外，STAT3 被鉴定为 RCC 细胞中 circNUP98 的诱导物。circNUP98 通过新型 STAT3/circNUP98/miR-567/PRDX3 轴发挥致癌基因的作用，这可能为 RCC 的治疗提供潜在的生物标志物和治疗靶点。
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