Let-7c-5p 通过下调免疫相关的 CDCA8 抑制肝癌。

Let-7c-5p down-regulates immune-related CDCA8 to inhibit hepatocellular carcinoma.

机构信息

Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, No. 218 Jixi Road, Hefei, 230022, China.

Department of Hepatobiliary-Pancreatic Surgery and Organ Transplantation Center, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, China.

出版信息

Funct Integr Genomics. 2023 Feb 4;23(1):56. doi: 10.1007/s10142-023-00974-9.

DOI:10.1007/s10142-023-00974-9

PMID:36737507

Abstract

OBJECTIVE

The aim of this study is to investigate the effect of let-7c-5p on the malignant behaviors of hepatocellular carcinoma (HCC) and its specific molecular pathway.

METHODS

Differential expression and survival analysis of let-7c-5p were obtained from The Cancer Genome Atlas database, and then its expression level was preliminarily verified through qPCR. The effect of let-7c-5p on the malignant phenotype of HCC cells was subsequently evaluated using CCK-8, transwell, wound healing, and flow cytometry assays. Downstream mRNA regulated by let-7c-5p was identified and confirmed by ENCORI database, dual-luciferase reporter, and western blot assays. The immunocorrelation of genes was evaluated by Xiantao tool, and TIMER and TISIDB databases.

RESULTS

The expression level of let-7c-5p in HCC was obviously reduced, which was found to be closely associated with the short survival time of HCC patients. Cell phenotypic experiments showed that let-7c-5p inhibited proliferation, invasion, and migration and promoted apoptosis of HCC cells. Dual-luciferase reporter and western blot analysis demonstrated that CDCA8 is a downstream mRNA of let-7c-5p and is negatively regulated by it. Rescue experiment revealed that CDCA8 reversed the effect of let-7c-5p on the malignant phenotype of HCC cells. Furthermore, analysis of the public database revealed that CDCA8 is related to some immune cells and immunomodulators, and that it may participate in the regulation of some immune pathways and immune functions.

CONCLUSION

Let-7c-5p has been proved to suppress HCC by down-regulating immune-related CDCA8, which will help understand the pathogenesis of HCC and develop drugs for its treatment.

摘要

目的

本研究旨在探讨 let-7c-5p 对肝细胞癌（HCC）恶性行为的影响及其特定分子途径。

方法

从癌症基因组图谱数据库中获取 let-7c-5p 的差异表达和生存分析，然后通过 qPCR 初步验证其表达水平。随后，通过 CCK-8、transwell、划痕愈合和流式细胞术实验评估 let-7c-5p 对 HCC 细胞恶性表型的影响。通过 ENCORI 数据库、双荧光素酶报告基因和 Western blot 实验鉴定和验证 let-7c-5p 下游调节的 mRNA。通过 Xiantao 工具、TIMER 和 TISIDB 数据库评估基因的免疫相关性。

结果

HCC 中 let-7c-5p 的表达水平明显降低，与 HCC 患者的短生存期密切相关。细胞表型实验表明，let-7c-5p 抑制 HCC 细胞的增殖、侵袭和迁移，促进其凋亡。双荧光素酶报告基因和 Western blot 分析表明，CDCA8 是 let-7c-5p 的下游 mRNA，受其负调控。挽救实验表明，CDCA8 逆转了 let-7c-5p 对 HCC 细胞恶性表型的影响。此外，对公共数据库的分析表明，CDCA8 与一些免疫细胞和免疫调节剂有关，可能参与调节一些免疫途径和免疫功能。