Circular RNA EGLN3 silencing represses renal cell carcinoma progression through the miR-1224-3p/HMGXB3 axis.

Renal cell carcinoma (RCC) is a common tumor of the urinary system, and its global incidence is increasing annually. Circular RNAs (circRNAs) are involved in RCC tumorigenesis; however, the role of circ-EGLN3 (hsa_circ_0031594) derived from the Egl nine homolog 3 (EGLN3) gene in RCC remains undetermined. Circ-EGNL3 expression was examined before and after RNase R and actinomycin treatments in RCC cells and tissues. Cell proliferation, migration, and invasion were assessed using the CCK-8 assay, EdU staining, and wound-healing and Transwell assays. The interactions between microRNA (miR)-1224-3p and circ-EGLN3, and between miR-1224-3p and HMG box domain containing 3 (HMGXB3) were predicted by bioinformatics analysis and validated by dual-luciferase reporter assay. Circ-EGLN3 was identified using RNase R and actinomycin treatments. Circ-EGLN3 was upregulated in RCC cells and tissues and correlated with poor overall survival. Silencing of circ-EGNL3 decreased RCC cell proliferation, migration, and invasion. Mechanistic studies indicated that circ-EGNL3 acts as a sponge for miR-1224-3p, which targeted HMGXB3. Circ-EGNL3 indirectly upregulated HMGXB3 by targeting miR-1224-3p, and overexpression of circ-EGLN3 reversed the repressive effects of miR-1224-3p on RCC. Circ-EGLN3 regulated RCC progression through the miR-1224-3p/HMGXB3 axis, suggesting its potential as a therapeutic target.

Zhang G ，Wang J ，Tan W ，Han X ，Han B ，Wang H ，Xia Y ，Sun Y ，Li H ... -  《-》

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

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.

Lin L ，Cai J 《-》

Circular RNA circSDHC serves as a sponge for miR-127-3p to promote the proliferation and metastasis of renal cell carcinoma via the CDKN3/E2F1 axis.

Cen J ，Liang Y ，Huang Y ，Pan Y ，Shu G ，Zheng Z ，Liao X ，Zhou M ，Chen D ，Fang Y ，Chen W ，Luo J ，Zhang J ... -  《Molecular Cancer》

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 ... -  《-》

Circular RNA hsa_circ_0054537 sponges miR-130a-3p to promote the progression of renal cell carcinoma through regulating cMet pathway.

Renal cell carcinoma (RCC) is one of the most common tumors of the urinary system, seriously impacting public health. CircRNAs have been indicated as potentially critical mediators in tumorigenesis and cancer progression. However, their specific role in the metastasis of RCC remains unclear. In present study, we identified that miR-130a-3p presented aberrantly low-level in RCC cells. Furthermore, it was demonstrated that upregulated miR-130a-3p suppressed the proliferation and migration of cell and promoted cell apoptosis in RCC. Then we predicted the underlyingly upstream modulator of miR-130a-3p was a novel circRNA hsa_circ_0054537, which exhibited dysregulated in RCC cells. Subsequently, we confirmed the direct interaction between hsa_circ_0054537 and miR-130a-3p by RNA pulldown assay. Additionally, luciferase assay confirmed the correlation between hsa_circ_0054537 and miR-130a-3p at the transcriptional level. We also found hsa_circ_0054537 could affect the tumorigenesis through binding to miR-130a-3p competitively. In addition, we identified the target of miR-130a-3p was oncogene cMet, which could be co-controlled by hsa_circ_0054537 and miR-130a-3p. In conclusion, we demonstrated that circRNA hsa_circ_0054537 functioned as a competitive endogenous RNA to regulate cMet expression via sponging miR-130a-3p in renal cancer.

Li R ，Luo S ，Zhang D 《-》