Department of Geriatric Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, China.
Department of General Practice, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, China.
BMC Urol. 2021 Mar 28;21(1):49. doi: 10.1186/s12894-021-00820-9.
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.
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.
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.
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.
透明细胞肾细胞癌（ccRCC）是一种特征明确且最常见的肾癌。本研究旨在探讨 let-7i-5p 在 ccRCC 细胞中的作用及其潜在机制。
通过生物信息学分析，我们研究了 let-7i-5p 在癌症基因组图谱（TCGA）数据库中的表达，并预测了 let-7i-5p 在 ccRCC 细胞中的生物学功能和可能的靶基因。通过细胞增殖试验、划痕愈合试验和 Transwell 侵袭试验来描述 let-7i-5p 对 ccRCC 细胞的影响。通过双荧光素酶报告基因试验、定量实时聚合酶链反应和 Western blot 检测来验证 let-7i-5p 与 HABP4 之间的相互作用。进行挽救实验来研究 let-7i-5p 与 HABP4 之间的关系。
TCGA 数据分析显示，ccRCC 组织中 let-7i-5p 的表达显著增加，且与总体生存不良显著相关。进一步验证表明，let-7i-5p 抑制剂可抑制 ccRCC 细胞增殖、迁移和侵袭，而 let-7i-5p 模拟物则增强其作用。随后，预测 HABP4 是 let-7i-5p 的靶基因。TCGA 数据显示，ccRCC 组织中 HABP4 的表达降低，且 HABP4 表达与 let-7i-5p 呈负相关。进一步验证表明，下调 HABP4 表达可促进细胞增殖、迁移和侵袭。双荧光素酶报告基因试验表明，let-7i-5p/HABP4 轴参与了 ccRCC 的发生。
我们的研究结果表明，let-7i-5p 在 ccRCC 中作为肿瘤促进因子发挥作用，并通过靶向 HABP4 促进细胞增殖、迁移和侵袭。这些结果阐明了 ccRCC 的发病机制，并为其治疗提供了潜在靶点。
