FBW7 介导的 CHD3 降解抑制肝癌转移和干性以增强奥沙利铂敏感性。

FBW7-Mediated Degradation of CHD3 Suppresses Hepatocellular Carcinoma Metastasis and Stemness to Enhance Oxaliplatin Sensitivity.

机构信息

Department of Ultrasound, The First Affiliated Hospital of Harbin Medical University, 150001 Harbin, Heilongjiang, China.

Department of Interventional Radiology, Harbin Medical University Cancer Hospital, 150081 Harbin, Heilongjiang, China.

出版信息

Front Biosci (Landmark Ed). 2024 Oct 16;29(10):357. doi: 10.31083/j.fbl2910357.

DOI:10.31083/j.fbl2910357

PMID:39473409

Abstract

BACKGROUND

Ubiquitination plays a key role in various cancers, and F-box and WD repeat domain containing 7 (FBW7) is a tumor suppressor that targets several cancer-causing proteins for ubiquitination. This paper set out to pinpoint the role of FBW7 in hepatocellular carcinoma (HCC).

METHODS

The target proteins of FBW7 and the expression of hromodomain helicase DNA binding protein 3 () were analyzed in liver HCC (LIHC) samples using the BioSignal Data website. The effects of CHD3 and FBW7 on HCC cell viability, migration, invasion and stemness were investigated through cell counting kit (CCK)-8, wound healing, transwell and sphere formation assays. Detection on CHD3 and FBW7 expressions as well as their relationship was performed employing quantitative reverse transcription-polymerase chain reaction (qRT-PCR), immunoprecipitation, ubiquitination and western blot analyses.

RESULTS

The prediction of Ubibrowser revealed CHD3 as a target protein of FBW7. The data of starBase exhibited a higher expression level of in LIHC samples relative to normal samples. was upregulated in HCC cells. knockdown inhibited HCC cell proliferation, migration, invasion, stemness and oxaliplatin sensitivity. FBW7 targeted CHD3 for ubiquitination. overexpression restrained HCC cell migration, invasion and stemness, and attenuated the effects of overexpressed on promoting migration, invasion, stemness and oxaliplatin resistance in HCC cells.

CONCLUSION

FBW7 overexpression suppresses HCC cell metastasis, stemness and oxaliplatin resistance via targeting CHD3 for ubiquitylation and degradation.

摘要

背景

泛素化在各种癌症中起着关键作用，而 F-box 和 WD 重复域包含 7（FBW7）是一种肿瘤抑制因子，可针对几种致癌蛋白进行泛素化。本文旨在确定 FBW7 在肝细胞癌（HCC）中的作用。

方法

使用 BioSignal Data 网站分析肝 HCC（LIHC）样本中 FBW7 的靶蛋白和染色质解旋酶 DNA 结合蛋白 3（）的表达。通过细胞计数试剂盒（CCK）-8、划痕愈合、Transwell 和球体形成测定法研究 CHD3 和 FBW7 对 HCC 细胞活力、迁移、侵袭和干性的影响。通过定量逆转录-聚合酶链反应（qRT-PCR）、免疫沉淀、泛素化和 Western blot 分析检测 CHD3 和 FBW7 的表达及其关系。

结果

Ubibrowser 的预测显示 CHD3 是 FBW7 的靶蛋白。starBase 的数据显示，与正常样本相比，LIHC 样本中表达水平更高。在 HCC 细胞中上调。沉默抑制 HCC 细胞增殖、迁移、侵袭、干性和奥沙利铂敏感性。FBW7 靶向 CHD3 进行泛素化。过表达抑制 HCC 细胞迁移、侵袭和干性，并减弱过表达对促进 HCC 细胞迁移、侵袭、干性和奥沙利铂耐药性的影响。