Circ_0008717 promotes renal cell carcinoma progression by upregulating FBXO17 via targeting miR-217.

Renal cell carcinoma (RCC) is a common lethal urological malignancy. Circular RNAs are assumed to play important roles in cancer development. The objective of the present study was to investigate the role and action mechanism of circ_0008717 in RCC. The expression of circ_0008717, miR-217 and F-box protein 17 (FBXO17) mRNA was detected by a real-time quantitative polymerase chain reaction. Cell proliferation was examined using a cell counting kit-8 assay and an 5-ethynyl-2'-deoxyuridine assay. Cell apoptosis was assessed by a flow cytometry assay. Cell migration and cell invasion were investigated using a transwell assay. Glycolysis progression was assessed according to the levels of glucose uptake and lactate production. The expression of glycolysis-related proteins and FBXO17 protein was quantified by western blotting. The targets were analyzed by the bioinformatics tools (starBase and circinteractome) and validated by a dual-luciferase reporter assay, RNA pull-down assay and RNA immunoprecipitation assay. A xenograft model was established to monitor the role of circ_0008717 in vivo. Circ_0008717 was upregulated in RCC tissues and cells. Silencing circ_0008717 suppressed RCC cell proliferation, migration, invasion and glycolysis but promoted cell apoptosis. MiR-217 was a target of circ_0008717 and bound to the FBXO17 3' untranslated region. The expression of FBXO17 was positively regulated by circ_0008717 but impaired by miR-217 reintroduction. The inhibitory effects of circ_0008717 knockdown on RCC cell malignant behaviors were reversed by miR-217 inhibition or FBXO17 overexpression. Circ_0008717 knockdown inhibited tumor growth in vivo by regulating miR-217 and FBXO17. Circ_0008717 aggravated the progression of RCC by activating FBXO17 through targeting miR-217, which provided a novel mechanism for circ_0008717 to participate in RCC progression.

Shen S ，Jiang M ，Deng W ，Liu X ，Xiong J ，Zeng Z ，Zhao H ，Zeng X ，Fu B ... -  《-》

Silencing circular RNA circ_0054537 and upregulating microRNA-640 suppress malignant progression of renal cell carcinoma via regulating neuronal pentraxin-2 (NPTX2).

Pei L ，Lv X ，Jia G ，Tan X ，Li M ，Zhang A ... -  《-》

Circ_0005875 sponges miR-502-5p to promote renal cell carcinoma progression through upregulating E26 transformation specific-1.

Increasing evidence has shown that circular RNAs (circRNAs) play critical roles in various cancers, including renal cell carcinoma (RCC). We aimed to explore the role and underlying mechanism of circ_0005875 in RCC. The expression levels of circ_0005875, microRNA-502-5p (miR-502-5p) and E26 transformation specific-1 (ETS1) mRNA were determined by quantitative real-time PCR. Cell proliferation was assessed by Cell Counting Kit-8, colony formation, and 5-Ethynyl-2'-deoxyuridine (EdU) assays. Cell migration and invasion were monitored by wound healing assay and transwell assay, respectively. Flow cytometry analysis was applied to determine cell apoptosis and cell cycle distribution. Western blot assay was performed to measure the protein expression of CyclinD1 and ETS1. The interaction between miR-502-5p and circ_0005875 or ETS1 was confirmed by dual-luciferase reporter and RNA immunoprecipitation assays. A xenograft tumor model was established to confirm the role of circ_0005875 in vivo. Circ_0005875 and ETS1 were upregulated and miR-502-5p was downregulated in RCC tissues and cells. Knockdown of circ_0005875 suppressed RCC cell proliferation, migration and invasion, and induced apoptosis and cell cycle arrest. MiR-502-5p was a target of circ_0005875, and miR-502-5p inhibition reversed the inhibitory effects of circ_0005875 knockdown on the malignant behaviors of RCC cells. ETS1 was a direct target of miR-502-5p, and miR-502-5p exerted its anti-tumor role in RCC cells by targeting ETS1. Moreover, circ_0005875 knockdown decreased ETS1 expression by sponging miR-502-5p. Additionally, circ_0005875 depletion suppressed tumor growth in vivo. Circ_0005875 knockdown suppressed RCC progression by regulating miR-502-5p/ETS1 axis, which might provide a promising therapeutic target for RCC.

Luo S ，Deng F ，Yao N ，Zheng F ... -  《-》

Circ_0000274 contributes to renal cell carcinoma progression by regulating miR-338-3p/NUCB2 axis and JAK1/STAT3 pathway.

Kidney transplant recipients (KTRs) are at increased risk of developing renal cell carcinoma (RCC). Accumulating evidence has demonstrated that circular RNAs (circRNAs) are essential players in tumor advancement. However, the functions of circ_0000274 in renal cell carcinoma (RCC) are barely explored. The primary RCC cell lines 786-O and A498 were used in this study. Quantitative real-time polymerase chain reaction (qRT-PCR) assay was employed for the RNA levels of circ_0000274, microRNA-338-3p (miR-338-3p) and nucleobindin 2 (NUCB2). RNase R assay was conducted to analyze the feature of circ_0000274.Cell Counting Kit-8 (CCK-8) assay, colony formation assay, transwell assay, tube formation assay and flow cytometry analysis were conducted for cell viability, colony formation, metastasis, angiogenesis and apoptosis, respectively. Western blot assay was utilized for protein levels. Dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were adopted to analyze the associations of circ_0000274 RNA, miR-338-3p RNA and NUCB2 protein. Murine xenograft model was established to explore the function of circ_0000274 RNA in vivo. Immunohistochemistry (IHC) assay was used to analyze NUCB2 protein level in xenograft tumors. Compared to normal tissues and cells, circ_0000274 RNA level was elevated in RCC tissues and cells. Knockdown of circ_0000274 RNA suppressed cell viability, colony formation, metastasis and tube formation and promoted apoptosis in RCC cells in vitro. Circ_0000274 RNA sponged miR-338-3p RNA to positively regulate NUCB2 protein in RCC cells. Inhibition of miR-338-3p reversed the impacts of circ_0000274 knockdown on RCC cell malignant behaviors. MiR-338-3p RNA overexpression repressed the malignant phenotypes of RCC cells, while NUCB2 protein elevation could abrogate the effect. Moreover, circ_0000274 RNA knockdown blocked tumorigenesis in vivo. Besides, circ_0000274 RNA knockdown inactivated the JAK1/STAT3 protein signaling pathway. Circ_0000274 RNA functioned as an oncogene in RCC development by regulating miR-338-3p RNA/NUCB2 protein axis and activating the JAK1/STAT3 protein signaling pathway.

Qi Q ，Sun Y ，Yang Y ，Liu Y ... -  《-》

Circ_0037866 Contributes to the Tumorigenesis of Renal Cell Carcinoma by Sequestering miR-384 to Elevate Chromobox 5 Expression.

Circular RNAs (circRNAs) were demonstrated to have roles in the carcinogenesis of renal cell carcinoma (RCC). Hence, this work aimed to determine the functions and molecular mechanism of circ_0037866 in regulating the progression of RCC. Quantitative real-time polymerase chain reaction and Western blotting were used to detect the levels of genes and proteins. In vitro assays, including colony formation, 5-ethynyl-2'-deoxyuridine, flow cytometry, transwell assays, and in vivo tumor formation, were conducted to investigate the effects of circ_0037866 on RCC tumorigenesis. Dual-luciferase reporter assay, RNA pull-down, and RNA immunoprecipitation assay were used to confirm the interaction between miR-384 and circ_0037866 or Chromobox 5 (CBX5). Circ_0037866 is a stable circRNA and was found to be increased in RCC tissues and cells. Functionally, circ_0037866 silencing suppressed RCC cell survival, invasion, and migration in vitro, and impeded RCC cell tumorigenesis in the subcutaneous xenograft model. Mechanistically, circ_0037866 could function as a sponge for miR-384 to elevate the expression of its target CBX5. Furthermore, a series of rescue experiments showed that miR-384 inhibition reversed the anticancer effects of circ_0037866 knockdown on RCC cells; besides that, miR-384 restoration suppressed RCC cell growth and mobility, which were attenuated by CBX5 overexpression. Circ_0037866 knockdown restrains the tumorigenesis of RCC by miR-384/CBX5, revealing a promising molecular target for RCC therapy.

Shi X ，Song S ，Gao Y ，Cui Z ，Wang W ，Liu M ... -  《-》