USP20 regulates the stability of EMT transcription factor SOX4 and influences colorectal cancer metastasis

IF 3.7 4区医学 Q2 PATHOLOGY

Pathology, research and practice Pub Date : 2022-05-01 Epub Date: 2022-04-04 DOI:10.1016/j.prp.2022.153879

Yu Guan, Shi-ru Jiang, Jun-guang Liu, Ji-rong Shi, Zhan-bing Liu

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引用次数: 2

Abstract

Background

Colorectal cancer (CRC) is a familiar malignancy accompanied by higher morbidity and mortality. The deubiquitination enzyme USP20 has been discovered to be one key factor in several cancers progression. SOX4 is a critical transcription factor to regulate the expression of various genes, and participates into the occurrence and progression of cancers. In this study, it was aimed to illustrate the role of USP20 and the regulatory relationship between USP20 and SOX4 in CRC.

Methods

The protein expressions of USP20, SOX4, E-cadherin, N-cadherin, Snail and slug were tested through western blot. The cell proliferation ability was verified through CCK-8 assay. The migration and invasion abilities were detected through Transwell assay. The mRNA expression of SOX4 was confirmed through RT-qPCR. The interaction between USP20 and SOX4 was notarized through Co-IP assay.

Result

Our study demonstrated that USP20 displayed higher expression, and facilitated CRC progression through regulating cell proliferation, migration, invasion and EMT process markers. USP20 was found to modulate SOX4 protein expression. Next, it was verified that USP20 regulated SOX4 degradation through deubiquitination. Finally, through rescue assays, we revealed that USP20 mediated SOX4 expression to accelerate CRC progression.

Conclusions

In this study, USP20 regulated the stability of EMT transcription factor SOX4 and aggravated colorectal cancer metastasis. This finding might highlight the function of USP20 in the treatment of CRC.

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USP20调控EMT转录因子SOX4的稳定性，影响结直肠癌的转移

结直肠癌(CRC)是一种常见的恶性肿瘤，发病率和死亡率都很高。去泛素化酶USP20已被发现是几种癌症进展的一个关键因素。SOX4是调控多种基因表达的关键转录因子，参与了癌症的发生和发展。本研究旨在阐明USP20在CRC中的作用以及USP20与SOX4之间的调控关系。方法采用western blot法检测USP20、SOX4、E-cadherin、N-cadherin、Snail和slug蛋白的表达。通过CCK-8实验验证细胞增殖能力。通过Transwell实验检测其迁移和侵袭能力。RT-qPCR证实SOX4 mRNA表达。通过Co-IP法验证了USP20与SOX4的相互作用。结果研究表明，USP20表达较高，并通过调节细胞增殖、迁移、侵袭和EMT过程标志物促进结直肠癌的进展。发现USP20可调节SOX4蛋白的表达。接下来，我们验证了USP20通过去泛素化调控SOX4的降解。最后，通过挽救实验，我们发现USP20介导SOX4表达加速CRC进展。结论在本研究中，USP20调节EMT转录因子SOX4的稳定性，加重结直肠癌转移。这一发现可能会突出USP20在治疗结直肠癌中的作用。

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

Pathology, research and practice 医学-病理学

CiteScore

5.00

自引率

3.60%

发文量

405

审稿时长

24 days

期刊介绍： Pathology, Research and Practice provides accessible coverage of the most recent developments across the entire field of pathology: Reviews focus on recent progress in pathology, while Comments look at interesting current problems and at hypotheses for future developments in pathology. Original Papers present novel findings on all aspects of general, anatomic and molecular pathology. Rapid Communications inform readers on preliminary findings that may be relevant for further studies and need to be communicated quickly. Teaching Cases look at new aspects or special diagnostic problems of diseases and at case reports relevant for the pathologist''s practice.