锌指蛋白300通过上调c-MYC基因表达促进肝细胞癌的增殖和迁移。
ZNF300 promotes proliferation and migration of hepatocellular carcinoma by upregulating c-MYC gene expression.
作者信息
Xiang Wei, Ni Junwei, Dong Liyang, Zhu Guoqing
机构信息
Department of Intervention, The First Affiliated Hospital of Wenzhou Medical University, Nanbaixiang Street, Ouhai District, Wenzhou, Zhejiang 325015, China.
Department of Intervention, The First Affiliated Hospital of Wenzhou Medical University, Nanbaixiang Street, Ouhai District, Wenzhou, Zhejiang 325015, China.
出版信息
Clin Res Hepatol Gastroenterol. 2024 Aug;48(7):102415. doi: 10.1016/j.clinre.2024.102415. Epub 2024 Jul 16.
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.
背景
肝细胞癌（HCC）是肝脏最常见的原发性恶性肿瘤。目前，HCC的治疗方法仅限于手术切除和肝移植，尚无有效的全身治疗方法。
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）转染到HCC细胞中，以增加或抑制ZNF300的表达。分别进行5 - 乙炔基 - 2'-脱氧尿苷检测（EdU）、细胞计数试剂盒 - 8检测（CCK - 8）和Transwell侵袭检测，以评估HCC细胞的增殖、活力、迁移和侵袭能力。通过蛋白质印迹法检测肿瘤迁移和侵袭相关蛋白（基质金属蛋白酶2（MMP - 2）和MMP - 9）、c - MYC以及MAPK/ERK信号通路相关分子（p - ERK1/2、ERK1/俯，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。测量肿瘤体积和重量。
结果
ZNF300在HCC组织和细胞中上调。转染ZNF300后HCC细胞中MMP - 2和MMP - 9的表达增加，而转染shZNF300的HCC细胞中其表达降低。ZNF300的下调抑制了HCC细胞的增殖、迁移和侵袭，而ZNF300的过表达则产生相反的效果。此外，ZNF300过表达后c - MYC和MAPK/ERK信号通路相关分子的表达增加，而ZNF300下调后则降低。在肿瘤异种移植实验中，ZNF300的下调降低了肿瘤体积和重量。
结论
本研究证明，ZNF300的下调通过降低c - MYC表达和MAPK/ERK信号通路来抑制HCC生长。
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