Abstract
BackgroundClear cell renal cell carcinoma (ccRCC) is one of the best-characterized and most pervasive renal cancers. The present study aimed to explore the effects and potential mechanisms of let-7i-5p in ccRCC cells.MethodsUsing bioinformatics analyses, we investigated the expression of let-7i-5p in The Cancer Genome Atlas (TCGA) database and predicted biological functions and possible target genes of let-7i-5p in ccRCC cells. Cell proliferation assay, wound healing assay and transwell invasion assay were conducted to characterize the effects of let-7i-5p in ccRCC cells. To verify the interactions between let-7i-5p and HABP4, dual-luciferase reporter assay, quantitative real-time polymerase chain reaction, and western blotting were conducted. Rescue experiments were used to investigate the relationship between let-7i-5p and HABP4.ResultsTCGA data analysis revealed that ccRCC tissues had significantly increased let-7i-5p expression, which was robustly associated with poor overall survival. Further verification showed that ccRCC cell proliferation, migration and invasion were inhibited by let-7i-5p inhibitor but enhanced by let-7i-5p mimics. Subsequently, HABP4 was predicted to be the target gene of let-7i-5p. TCGA data showed that ccRCC tissues had decreased expression of HABP4 and that HABP4 expression was negatively correlated with let-7i-5p. Further verification showed that downregulation of HABP4 expression promoted cell proliferation, migration and invasion. The dual-luciferase reporter gene assay suggested that the let-7i-5p/HABP4 axis was responsible for the development of ccRCC.ConclusionOur results provide evidence that let-7i-5p functions as a tumor promoter in ccRCC and facilitates cell proliferation, migration and invasion by targeting HABP4. These results clarify the pathogenesis of ccRCC and offer a potential target for its treatment.
Highlights
Clear cell renal cell carcinoma is one of the best-characterized and most pervasive renal cancers
This study explored the function of Hyaluronan-binding protein 4 (HABP4) in Clear cell renal cell carcinoma (ccRCC) and the negative regulatory relationship between let-7i-5p and HABP4 to further our understanding of the molecular mechanism underlying ccRCC tumorigenesis and offer a potential target for ccRCC therapies
Using RNAseq (IlluminaHiseq), let-7i-5p expression was measured in 70 normal samples and 494 primary ccRCC tumor samples, whereas HABP4 expression was measured in 72 normal samples and 533 primary ccRCC tumors
Summary
Clear cell renal cell carcinoma (ccRCC) is one of the best-characterized and most pervasive renal cancers. The present study aimed to explore the effects and potential mechanisms of let-7i-5p in ccRCC cells. Renal cell carcinoma (RCC), one of the most common urological tumors, can be categorized into nonclear cell renal cell carcinoma (nccRCC) and clear cell renal cell carcinoma (ccRCC) based on cytogenetic and. Given that most patients with ccRCC are not sensitive to chemotherapy or radiation, surgical treatment has remained most effective [5, 6]. Exploring the molecular mechanisms underlying the development of ccRCC and identifying effective treatment strategies to. Let-7, one of the first miRNAs to be discovered, has been found to be highly conserved and widely expressed among species [9, 10]. The role of let-7i-5p in ccRCC has yet to be studied
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