To elucidate the clinical significance, biological functions, and molecular mechanisms of circEVI5 in renal cell carcinoma (RCC) pathogenesis.
Approach:
Expression Profiling: CircEVI5 expression was screened using GEO and TCGA-KIRC datasets, and verified in RCC cell lines and normal renal tubular epithelial cells via qRT-PCR.
Functional Assays: CCK-8, Transwell assays, and a subcutaneous xenograft model were used to assess circEVI5's role in proliferation, migration, and invasion.
Molecular Interaction Studies: RNA pull-down, RIP, and dual-luciferase reporter assays validated interactions among circEVI5, miR-433, and GBP2.
Clinical Correlation Analysis: Clinical correlations were analyzed based on TCGA datasets and immunohistochemical staining results.
Key Findings:
CircEVI5 was significantly upregulated in RCC tissues and cell lines, correlating with advanced tumor stage and poor survival.
Knockdown of circEVI5 inhibited cell viability, migration, and invasion in vitro and suppressed tumor growth in vivo.
CircEVI5 acted as a sponge for miR-433, which was downregulated in RCC and inversely correlated with GBP2 expression.
GBP2 overexpression in RCC tissues predicted reduced survival, and miR-433 levels were inversely correlated with both circEVI5 and GBP2.
Interpretation:
CircEVI5 is established as an oncogenic driver in RCC progression through the miR-433/GBP2 regulatory axis.
Limitations:
The study primarily focused on in vitro and xenograft models, which may not fully replicate human RCC biology.
Further clinical validation is needed to confirm the prognostic value of circEVI5 in RCC patients.
Conclusion:
CircEVI5 may serve as a prognostic biomarker for RCC patients and represents a potential therapeutic target.
