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

IF 3.3 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Frontiers in bioscience (Landmark edition) Pub Date : 2024-10-16 DOI:10.31083/j.fbl2910357

Shijie Li, Tingting Fan, Changjun Wu

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引用次数: 0

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 (CHD3) 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 CHD3 in LIHC samples relative to normal samples. CHD3 was upregulated in HCC cells. CHD3 knockdown inhibited HCC cell proliferation, migration, invasion, stemness and oxaliplatin sensitivity. FBW7 targeted CHD3 for ubiquitination. FBW7 overexpression restrained HCC cell migration, invasion and stemness, and attenuated the effects of overexpressed CHD3 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.

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FBW7介导的CHD3降解抑制肝细胞癌转移和干细胞形成，从而提高奥沙利铂的敏感性

背景：泛素化在各种癌症中起着关键作用，而含有F-box和WD重复域的7（FBW7）是一种肿瘤抑制因子，可靶向多种致癌蛋白进行泛素化。本文旨在明确 FBW7 在肝细胞癌（HCC）中的作用：方法：利用生物信号数据网站分析了肝脏HCC（LIHC）样本中FBW7的靶蛋白和色域螺旋酶DNA结合蛋白3（CHD3）的表达。通过细胞计数试剂盒（CCK）-8、伤口愈合、跨孔和球形成试验研究了CHD3和FBW7对HCC细胞活力、迁移、侵袭和干性的影响。通过定量反转录聚合酶链反应（qRT-PCR）、免疫沉淀、泛素化和免疫印迹分析检测了CHD3和FBW7的表达及其关系：Ubibrowser的预测结果显示CHD3是FBW7的靶蛋白。starBase 数据显示，与正常样本相比，CHD3 在 LIHC 样本中的表达水平更高。CHD3 在 HCC 细胞中上调。敲除 CHD3 可抑制 HCC 细胞的增殖、迁移、侵袭、干性和奥沙利铂敏感性。FBW7靶向CHD3进行泛素化。FBW7 的过表达抑制了 HCC 细胞的迁移、侵袭和干性，并减弱了过表达的 CHD3 对 HCC 细胞迁移、侵袭、干性和奥沙利铂耐药性的促进作用：结论：FBW7的过表达通过靶向CHD3的泛素化和降解抑制了HCC细胞的转移、干性和奥沙利铂耐药性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Frontiers in bioscience (Landmark edition)

CiteScore

3.50

自引率

0.00%

发文量