Angiopoietin-Related Protein 4-Transcript 3 Increases the Proliferation, Invasion, and Migration of Hepatocellular Carcinoma Cells and Inhibits Apoptosis.

DNA and cell biology Pub Date : 2024-04-01 Epub Date: 2024-03-11 DOI:10.1089/dna.2023.0392
Yun Bai, Guanghua Cui, Xiaoke Sun, Meiqi Wei, Yanying Liu, Jialu Guo, Yu Yang
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Abstract

To investigate the functional differences of angiopoietin-related protein 4 (ANGPTL4) transcripts in hepatocellular carcinoma (HCC) cells. By transfecting ANGPTL4-Transcript 1 and ANGPTL4-Transcript 3 overexpression vectors into HepG2 and Huh7 cell lines with ANGPTL4 knockdown, the effects of overexpression of two transcripts on cell viability, invasion, migration, and apoptosis were analyzed. The expression of two transcripts was compared in human liver cancer tissue, and their effects on tumor development were validated in vivo experiments in mice. Compared with control, the overexpression of ANGPTL4-Transcript 1 had no significant effect on viability, invasion, healing, and apoptosis of HepG2 and Huh7 cells. However, these two cell lines overexpressing ANGPTL4-Transcript 3 showed remarkably enhanced cell viability, invasive and healing ability, and decreased apoptosis ability. Furthermore, the mRNA level of ANGPTL4-Transcript 3 was significantly increased in human HCC tissues and promoted tumor growth compared with Transcript 1. Different transcripts of gene ANGPTL4 have distinct effects on HCC. The abnormally elevated Transcript 3 with the specific ability of promoting HCC proliferation, infiltration, and migration is expected to become a new biological marker and more precise intervention target for HCC.

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血管生成素相关蛋白 4 转录本 3 增加肝细胞癌细胞的增殖、侵袭和迁移并抑制细胞凋亡
研究肝细胞癌(HCC)细胞中血管生成素相关蛋白 4(ANGPTL4)转录本的功能差异。通过将 ANGPTL4-Transcript 1 和 ANGPTL4-Transcript 3 过表达载体转染到 ANGPTL4 基因敲除的 HepG2 和 Huh7 细胞系中,分析两种转录本的过表达对细胞活力、侵袭、迁移和凋亡的影响。比较了两种转录本在人肝癌组织中的表达情况,并在小鼠体内实验中验证了它们对肿瘤发生的影响。与对照组相比,过表达 ANGPTL4 转录本 1 对 HepG2 和 Huh7 细胞的活力、侵袭、愈合和凋亡没有明显影响。然而,过表达 ANGPTL4-Transcript 3 的这两种细胞株的细胞活力、侵袭和愈合能力明显增强,细胞凋亡能力下降。此外,与转录本 1 相比,ANGPTL4-转录本 3 在人类 HCC 组织中的 mRNA 水平明显升高,并促进了肿瘤的生长。基因 ANGPTL4 的不同转录本对 HCC 有不同的影响。异常升高的转录本3具有促进HCC增殖、浸润和迁移的特异性能力,有望成为HCC新的生物学标志物和更精确的干预靶点。
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