ZNF143 介导的 MEX3C 上调会促进肝细胞癌的进展。

IF 2.6 4区医学 Q2 GASTROENTEROLOGY & HEPATOLOGY

Clinics and research in hepatology and gastroenterology Pub Date : 2024-10-31 DOI:10.1016/j.clinre.2024.102492

Lili Zhang , Nan Dang , Jiongyi Wang , Wenying Zhang , Xiaohua Hu , Bin Jiang , Dan Zhao , Feng Liu , Haihua Yuan

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引用次数: 0

摘要

背景：微血管侵犯与肝细胞癌（HCC）患者的侵袭性肿瘤行为和复发密切相关。锌指蛋白 143（ZNF143）是一种转录因子，参与多种生理和发育过程。本研究主要关注 ZNF143 在 HCC 迁移和侵袭中的确切生物学作用和机制：方法：分析 ZNF143 在 HCC 患者中的表达和预后。方法：分析了 ZNF143 在 HCC 患者中的表达和预后，并通过 Western 印迹和反转录定量聚合酶链反应（RT-qPCR）对 ZNF143、mex-3 RNA 结合家族成员 C（MEX3C）的水平进行了定量。通过伤口愈合试验检测细胞迁移能力。Matrigel transwell 试验用于评估 HCC 细胞的侵袭能力。通过 mRNA 图谱分析筛选 ZNF143 过表达和敲除的差异表达基因。通过双荧光素酶检测来确定MEX3C的启动子活性。染色质免疫沉淀（ChIP）测定了ZNF143在MEX3C启动子上的富集：结果：ZNF143在HCC组织中过表达，其过表达与较差的预后相关，尤其是在肿瘤分级较高和微血管侵犯较多的HCC患者中。mRNA分析表明，ZNF143能显著上调MEX3C。ZNF143与HCC组织中MEX3C的表达呈正相关。ZNF143通过直接结合到MEX3C的启动子来激活MEX3C的转录。MEX3C敲除抑制了ZNF143过表达诱导的HCC细胞迁移和侵袭：结论：ZNF143通过与MEX3C启动子结合并激活其表达，促进了HCC细胞的迁移和侵袭。

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ZNF143-mediated upregulation of MEX3C promotes hepatocellular carcinoma progression

Background

Microvascular invasion is strongly associated with aggressive tumor behavior and recurrence in hepatocellular carcinoma (HCC) patients. Zinc finger protein 143(ZNF143) is a transcription factor involved in a wide variety of physiological and developmental processes. This study primarily focuses on the exact biological role and mechanism of ZNF143 in HCC migration and invasion.

Methods

The expression and prognosis of ZNF143 in HCC patients were analyzed. The levels of ZNF143, mex-3 RNA binding family member C (MEX3C) were quantified by western blot and reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Cell migration ability was detected by wound- healing assay. Matrigel transwell assay was conducted to evaluate the invasion of HCC cells. The differential expression genes of ZNF143 overexpression and knockdown were screened by mRNA profiling analysis. Dual luciferase assay was performed to determine the promoter activity of MEX3C. The enrichment of ZNF143 at MEX3C promoter was determined by chromatin immunoprecipitation (ChIP).

Results

ZNF143 is overexpressed in HCC tissues and that its overexpression is correlated with poorer prognosis, especially in HCC patients with higher tumor grades and microvascular invasion. Gain- and loss-of function experiments showed that ZNF143 promotes migration and invasion in HCC cells. mRNA profiling showed that ZNF143 significantly upregulates MEX3C. ZNF143 was positively correlated with MEX3C expression in HCC tissue. ZNF143 activates MEX3C transcription by directly binding to its promoter. MEX3C knockdown inhibited migration and invasion induced by ZNF143 overexpression in HCC cells.

Conclusion

ZNF143 promotes HCC cell migration and invasion by binding to MEX3C promoter and activating its expression.

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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.