ZNF300 promotes proliferation and migration of hepatocellular carcinoma by upregulating c-MYC gene expression

IF 2.6 4区医学 Q2 GASTROENTEROLOGY & HEPATOLOGY Clinics and research in hepatology and gastroenterology Pub Date : 2024-07-16 DOI:10.1016/j.clinre.2024.102415

Wei Xiang, Junwei Ni, Liyang Dong, Guoqing Zhu

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Abstract

Background

Hepatocellular carcinoma (HCC) is the most common primary malignant tumor of the liver. Currently, the treatments of HCC are limited to surgical resection and liver transplantation, and there is no effective systemic therapy.

Objectives

To investigate the regulatory mechanism of zinc finger protein 300 (ZNF300) in hepatocellular carcinoma (HCC).

Methods

The expressions of ZNF300 in HCC tissue samples and HCC cell lines (Hep3B, Huh7, SNU-387) were detected. ZNF300 overexpression vector (ZNF300) or shRNAZNF300 (shZNF300) was transfected into HCC cells to increase or inhibit ZNF300 expression. 5‐Ethynyl‐2′‐deoxyuridine assay (EdU), cell counting kit‐8 assay (CCK‐8) and transwell invasion assay were conducted to evaluate the proliferation, viability, migration, and invasion of HCC cells respectively. The expressions of tumor migration and invasion related proteins (matrix metallopeptidase 2 (MMP-2) and MMP-9), c-MYC, and MAPK/ERK signaling pathway related molecules (p-ERK1/2, ERK1/2, p-P38, P38) were determined by western blotting. Hep3B cells transfected with shZNF300 were subcutaneously injected into nude mice to perform tumor xenograft experiment. Tumor volume and weight were measured.

Results

ZNF300 was upregulated in HCC tissues and cells. The expressions of MMP-2 and MMP-9 were increased in HCC cells after transfecting with ZNF300 but reduced in HCC cells transfected with shZNF300. Downregulation of ZNF300 inhibited HCC cell proliferation, migration, and invasion, while overexpression of ZNF300 showed the opposite effects. Moreover, the expressions of c-MYC and MAPK/ERK signaling pathway related molecules were increased after overexpression of ZNF300 but reduced after downregulating ZNF300. In tumor xenograft experiment, downregulation of ZNF300 reduced tumor volume and weight.

Conclusion

The present study proved that downregulation of ZNF300 inhibited HCC growth by reducing c-MYC expression and MAPK/ERK signaling pathway.

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ZNF300 通过上调 c-MYC 基因表达促进肝细胞癌的增殖和迁移

背景肝细胞癌（HCC）是肝脏最常见的原发性恶性肿瘤。目的研究锌指蛋白 300（ZNF300）在肝细胞癌（HCC）中的调控机制。方法检测 ZNF300 在 HCC 组织样本和 HCC 细胞系（Hep3B、Huh7、SNU-387）中的表达。将 ZNF300 过表达载体（ZNF300）或 shRNAZNF300（shZNF300）转染至 HCC 细胞，以增加或抑制 ZNF300 的表达。5-Ethynyl-2′-deoxyuridine assay (EdU), cell counting kit-8 assay (CCK-8) and transwell invasion assay were conducted to evaluate the proliferation, viability, migration, and invasion of HCC cells respectively.用 Western 印迹法测定了肿瘤迁移和侵袭相关蛋白（基质金属肽酶 2（MMP-2）和 MMP-9）、c-MYC 和 MAPK/ERK 信号通路相关分子（p-ERK1/2、ERK1/2、p-P38、P38）的表达。将转染 shZNF300 的 Hep3B 细胞皮下注射到裸鼠体内，进行肿瘤异种移植实验。结果ZNF300在HCC组织和细胞中上调。转染 ZNF300 的 HCC 细胞中 MMP-2 和 MMP-9 的表达增加，而转染 shZNF300 的 HCC 细胞中 MMP-2 和 MMP-9 的表达减少。ZNF300的下调抑制了HCC细胞的增殖、迁移和侵袭，而ZNF300的过表达则表现出相反的效果。此外，过表达 ZNF300 后，c-MYC 和 MAPK/ERK 信号通路相关分子的表达增加，而下调 ZNF300 后，这些分子的表达减少。在肿瘤异种移植实验中，下调 ZNF300 可减少肿瘤体积和重量。

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来源期刊

Clinics and research in hepatology and gastroenterology GASTROENTEROLOGY & HEPATOLOGY-

CiteScore

4.30

自引率

3.70%

发文量

198

审稿时长

42 days

期刊介绍： Clinics and Research in Hepatology and Gastroenterology publishes high-quality original research papers in the field of hepatology and gastroenterology. The editors put the accent on rapid communication of new research and clinical developments and so called "hot topic" issues. Following a clear Editorial line, besides original articles and case reports, each issue features editorials, commentaries and reviews. The journal encourages research and discussion between all those involved in the specialty on an international level. All articles are peer reviewed by international experts, the articles in press are online and indexed in the international databases (Current Contents, Pubmed, Scopus, Science Direct). Clinics and Research in Hepatology and Gastroenterology is a subscription journal (with optional open access), which allows you to publish your research without any cost to you (unless you proactively chose the open access option). Your article will be available to all researchers around the globe whose institution has a subscription to the journal.