■已发现小脑5的锌指(ZIC5)在多种肿瘤中异常表达。本研究旨在揭示ZIC5在肝细胞癌中的表达及其作用机制。
■ZIC5在各种肿瘤中的表达及其与存活的关系的分析来源于癌症基因组图谱(TCGA)数据库。进行细胞计数试剂盒-8(CCK-8)和集落形成测定以检测HCC细胞增殖。通过RNA测序确定Huh1细胞中ZIC5过表达后的差异表达基因(DEGs)。Westernblot检测c-Myc蛋白水平,Bcl2,p21,E-cadherin,N-钙黏着蛋白,波形蛋白,和I型胶原α1(COL1A1)。
■在各种肿瘤组织中观察到ZIC5的表达急剧增加,包括HCC。Pearson相关分析显示,肝癌组织中ZIC5mRNA水平与MKI67mRNA水平呈正相关。具有高ZIC5表达的患者具有较短的总体存活时间。此外,ZIC5过表达促进HCC细胞增殖。然后,我们发现COL1A1被ZIC5过表达显著上调以促进细胞增殖,迁移,和肝癌细胞的侵袭。
■ZIC5可以加速增殖,迁移,通过上调COL1A1对肝癌细胞的侵袭。这是ZIC5和COL1A1有内在联系的第一份报告,为后续HCC研究拓展新的研究思路。
UNASSIGNED: Zinc finger of the cerebellum 5 (ZIC5) has been found to be abnormally expressed in a variety of tumors. This study aimed to reveal the expression and functional mechanism of ZIC5 in hepatocellular carcinoma (HCC).
UNASSIGNED: Analysis of ZIC5 expression in various tumors and its relationship with survival were derived from The Cancer Genome Atlas (TCGA) database. Cell counting kit-8 (CCK-8) and colony formation assays were performed for the detection of HCC cell proliferation. Differentially expressed genes (DEGs) after ZIC5 overexpression in Huh1 cells were determined by RNA sequencing. Western blot assays were conducted to detect the protein levels of c-Myc, Bcl2, p21, E-cadherin, N-cadherin, vimentin, and collagen type I alpha 1 (COL1A1).
UNASSIGNED: Dramatically increased expression of ZIC5 was observed in various tumor tissues, including HCC. Pearson\'s correlation analysis revealed that the mRNA levels of ZIC5 had a positive correlation with the mRNA levels of MKI67 in HCC tissues. Patients with high ZIC5 expression had a shorter overall survival time. Moreover, ZIC5 overexpression promoted HCC cell proliferation. Then, we found that COL1A1 was significantly upregulated by ZIC5 overexpression to promote the proliferation, migration, and invasion of HCC cells.
UNASSIGNED: ZIC5 could accelerate the proliferation, migration, and invasion of HCC cells through upregulating COL1A1. This is the first report that ZIC5 and COL1A1 are intrinsically linked, expanding new research ideas for subsequent HCC research.