UBE2C regulating the lung carcinoma progression via inhibiting ubiquitin-proteasomal degradation to increase MMP9 protein stability.

IF 1.6 4区生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY

Genes & genomics Pub Date : 2025-06-01 Epub Date: 2025-02-20 DOI:10.1007/s13258-025-01623-0

Jie Zhao, Juanjuan Dai, Ning Zhou, Dongqin Liu, Dandan Wang, Shuang Miao, Chao Liang, Di An, Jiatong Jiang, Kaikai Gong, Yan Wu

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引用次数: 0

Abstract

Background: Non-small-cell-lung-cancer (NSCLC) is a prevalent lung malignancy among humans. UBE2C is a critical component of the ubiquitin-proteasome system, and its expression level is significantly associated with cancer development and cell proliferation. Nevertheless, the mechanisms of UBE2C in NSCLC remain unclear.

Objective: We aimed to investigate the role of MMP9 in UBE2C-overexpressed NSCLC progression.

Methods: The GEPIA database and Kaplan-Meier curves were used to determine UBE2C expression in human tumors and survival in NSCLC. CCK8, colony formation, and Transwell^® assays were employed to assess the function of UBE2C in vitro. Western blotting, immunofluorescence assay, and RT-qPCR were utilized to determine protein and mRNA expression levels. CHX chase and co-immunoprecipitation assays were used to elucidate the regulatory mechanism.

Results: This research proved that UBE2C expression was related to patient overall survival, cell proliferation and migration. Furthermore, overexpressed UBE2C could promote the protein stability of Matrix metalloproteinase-9 (MMP9) to upregulate its protein level in NSCLC cells. Meanwhile, UBE2C upregulation promoted lung carcinoma progression by modulating MMP9 expression.

Conclusions: Our findings indicate that UBE2C may be a therapeutic and prognostic target for lung carcinoma.

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UBE2C通过抑制泛素-蛋白酶体降解提高MMP9蛋白稳定性来调节肺癌进展。

背景：非小细胞肺癌（NSCLC）是人类常见的肺部恶性肿瘤。UBE2C是泛素-蛋白酶体系统的关键组成部分，其表达水平与癌症的发生和细胞增殖显著相关。然而，UBE2C在非小细胞肺癌中的作用机制尚不清楚。目的：我们旨在研究MMP9在ube2c过表达的非小细胞肺癌进展中的作用。方法：采用GEPIA数据库和Kaplan-Meier曲线检测UBE2C在人肿瘤中的表达和NSCLC患者的生存率。采用CCK8、菌落形成和Transwell®检测来评估UBE2C的体外功能。Western blotting、免疫荧光法和RT-qPCR检测蛋白和mRNA的表达水平。采用CHX追踪和共免疫沉淀实验来阐明其调控机制。结果：本研究证实UBE2C表达与患者总体生存、细胞增殖和迁移有关。此外，过表达UBE2C可促进基质金属蛋白酶-9 （Matrix metalloproteinase-9, MMP9）的蛋白稳定性，上调其在NSCLC细胞中的蛋白水平。同时，UBE2C上调通过调节MMP9的表达促进肺癌的进展。结论：我们的研究结果表明，UBE2C可能是肺癌的治疗和预后靶点。

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

Genes & genomics 生物-生化与分子生物学

CiteScore

3.70

自引率

4.80%

发文量

131

审稿时长

6-12 weeks

期刊介绍： Genes & Genomics is an official journal of the Korean Genetics Society (http://kgenetics.or.kr/). Although it is an official publication of the Genetics Society of Korea, membership of the Society is not required for contributors. It is a peer-reviewed international journal publishing print (ISSN 1976-9571) and online version (E-ISSN 2092-9293). It covers all disciplines of genetics and genomics from prokaryotes to eukaryotes from fundamental heredity to molecular aspects. The articles can be reviews, research articles, and short communications.