A novel circRNA, circNUP98, a potential biomarker, acted as an oncogene via the miR‐567/ PRDX3 axis in renal cell carcinoma

Abstract

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.

Synergistic Effects of TW-37 and ABT-263 on Renal Cell Carcinoma Cells

“…Cell viabilities were performed as described. 19 In short, cells were seeded at a density of 2×10 4 cells/well in 96-well plates. 10 μL of 5 mg/mL MTT solution (Beyotime, Beijing, China) was added into each well and the absorbance was read by a microplate reader (BioTek, USA).…”

Role of Circular RNA in Kidney-Related Diseases

“…Gpnmb Naglu NF-κB activation Inflammation circ_0114427 (Cao et al, 2020) miR-494 AFT3 NF-κB activation circ-AKT3 (Xu et al, 2020) miR-144-5p Wnt/β-catenin pathway Wnt/β-catenin activation circ-YAP1 (Huang et al, 2020) miR-21-5p PI3K/AKT/mTOR pathway PI3K/AKT/mTOR activation circ-VMA21 (Shi et al, 2020) miR-9-3p SMG1 Oxidative stress Chronic kidney disease circHLA-C (Luan et al, 2018) miR-150 Undefined Fibrosis-associated genes express circRNA_15698 (Hu et al, 2019) miR-185 TGF-β1 Extracellular matrix-related protein synthesis circ_WBSCR17 (Li et al, 2020a) miR-185-5p SOX6 ECM accumulation circRNA_002453 (Ouyang et al, 2018) Undefined Undefined Biomarker in blood circ_DLGAP4 (Bai et al, 2020) miR-145 ERBB3/NF-κB/MMP-2 pathway Inflammation circLRP6 miR-205 HMGB 1/TLR4/NF-κB pathway Inflammation circRNA_010383 (Peng et al, 2020) miR-135a TRPC1 ECM accumulation circ-AKT3 (Tang et al, 2020) miR-296-3p E-cadherin ECM accumulation circNr1h4 (Lu et al, 2020) miR-155-5p Far1 Reactive oxygen cANRIL (Deng et al, 2019) miR-9 NF-κB and JNK/p38 pathways Inflammation Renal cell carcinom has_circ_001895 miR-296-5p SOX12 Promoting proliferation, migration, invasion, inhibiting apotosis circEGLN3 (Lin and Cai, 2020) miR-1299 IRF7 Promoting proliferation, migration, invasion, inhibiting apotosis circNRIP1 (Dong et al, 2020) miR-505 AMPK and PI3KL/AKT/mTOR pathways Promoting proliferation, migration, invasion, inhibiting apotosis circNUP98 (Yu et al, 2020) miR-567 PRDX3 Promoting proliferation, migration, invasion, inhibiting apotosis has_circ_0072309 miR-100 PI3KL/AKT/mTOR Inhibiting proliferation, migration, invasion, promoting apotosis circC3P1 miR-21/PTEN PI3K/AKT and NF-κB Inhibiting proliferation, migration, invasion, promoting apotosis circFNDC3B miR-99a JAK1/STAT3 and MEK/ERK pathways Promoting proliferation, migration circ-ZNF652 (Zhang and Guo, 2020) miR-205 JAK1/STAT3 and MEK/ERK pathways Promoting proliferation, migration circ-ZNF609 (Xiong et al, 2019) miR-138-5p FOXP4 Promoting proliferation, invasion circDHX33 (Wang et al, 2020) miR-498-3p MERK Promoting proliferation, invasion circHIPK3 miR-508-3p CXCL13 Promoting proliferation, migration, invasion circUBAP2 (Sun et al, 2020) miR-148a-3p FOXK2 Promoting proliferation, migration, invasion circ_001842 (Zeng et al, 2020) miR-502-5p SLC39A14 Promoting proliferation, migration, invasion cRAPGEF5 miR-27a-3p TXNIP Inhibiting proliferation, migration has_circ_0001451 associated genes (Zhou et al, 2013;…”

“…The increased circ-ZNF652 has the similar effect by sponging with miR-205 ( Zhang and Guo, 2020 ). It is also found that circNUP98 is under the regulation of STAT3, and it functions as a sponge of miR-567 and promotes the expression of PRDX3 (an antioxidant protein, belongs to the peroxiredoxins), leading to RCC progression ( Cox et al, 2009 ; Yu et al, 2020 ).…”

Circular RNA circUbe2k promotes hepatic fibrosis via sponging miR‐149‐5p/TGF‐β2 axis

“…Although discovery of circRNAs was exposed more than 20 years ago, for many years they were thought to be functionless byproducts of mRNA splicing 11,12 . Recently, many researches reveal that circRNAs play a critical role in the diagnosis and prognosis of various diseases 13,14 . It is reported that circRNA is characterized by covalently closed loop structures neither 5′ to 3′ polarity nor a polyadenylated tail, 15 is single‐stranded transcripts generated via back‐splicing 16 .…”