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Let-7i-5p enhances cell proliferation, migration and invasion of ccRCC by targeting HABP4
Yujie Liu1, Xing Hu2, Liang Hu3
1Department of Geriatric Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, China.
Background:
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.
Methods:
Using 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.
Results:
TCGA 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.
Conclusion:
Our 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.
Insights
let-7i-5p promotes clear cell renal cell carcinoma (ccRCC) progression by increasing cell proliferation, migration, and invasion. This microRNA targets HABP4, offering a potential therapeutic target for ccRCC treatment.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Clear cell renal cell carcinoma (ccRCC) is a prevalent kidney cancer.
- Understanding the molecular mechanisms driving ccRCC is crucial for effective treatment strategies.
Purpose of the Study:
- To investigate the role and underlying mechanisms of let-7i-5p in ccRCC.
- To identify potential therapeutic targets for ccRCC based on let-7i-5p function.
Main Methods:
- Bioinformatic analysis of The Cancer Genome Atlas (TCGA) database for let-7i-5p expression and targets.
- In vitro assays including proliferation, wound healing, and Transwell invasion assays.
- Dual-luciferase reporter assays, qRT-PCR, and Western blotting to confirm let-7i-5p and HABP4 interaction.
Main Results:
- let-7i-5p expression is elevated in ccRCC and associated with poor survival.
- let-7i-5p inhibition suppressed, while mimics enhanced, ccRCC cell proliferation, migration, and invasion.
- HABP4 was identified as a direct target of let-7i-5p, with its expression decreased in ccRCC and negatively correlated with let-7i-5p levels.
- Downregulation of HABP4 promoted ccRCC cell proliferation, migration, and invasion.
Conclusions:
- let-7i-5p acts as a tumor promoter in ccRCC by targeting HABP4.
- The let-7i-5p/HABP4 axis plays a significant role in ccRCC pathogenesis.
- Targeting the let-7i-5p/HABP4 pathway presents a potential therapeutic strategy for ccRCC.
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