编程细胞死亡6（PDCD6）是一种钙离子结合蛋白，在各种肿瘤中均有异常表达。本研究旨在探索PDCD6在肝细胞癌（HCCs）中的作用和机制。通过生物信息学和Western blotting分析肝癌患者和HCC细胞系中PDCD6的表达水平，并使用甲基噻唑四唑（MTT）和transwell分别测量细胞活力和转移能力。Western blotting用于测试HCC细胞系中相关生物标志物和分子通路因子。使用LY294002，一种抑制AKT的PI3K抑制剂，抑制AKT/GSK3β/β-catenin通路，以评估该通路在PDCD6与HCC癌发作之间的作用。癌症基因组图谱数据库分析表明，高PDCD6表达水平与肝癌进展相关。这与我们发现的HCC细胞系中PDCD6表达水平高于正常肝细胞系的结果是一致的。MTT、transwell迁移和Western blotting实验的结果表明，PDCD6的过表达正向调节HCC细胞的增殖、迁移和侵袭。相反，在AKT抑制剂存在的情况下，PDCD6表达上调抑制了HCC的细胞增殖、迁移和侵袭。此外，PDCD6通过上皮间充质转化促进HCC的细胞迁移和侵袭。机制研究证明，PDCD6通过AKT/GSK3β/β-catenin通路在HCC中作为肿瘤促进剂，增加了转录因子和细胞增殖和转移的表达。PDCD6在HCC中具有肿瘤刺激作用，介导了AKT/GSK3β/β-catenin信号传导，并可能成为HCC进展的潜在靶点。 版权所有© 2023年中国疾病预防控制中心出版社生物医学和环境科学编辑委员会。保留所有权利。

Programmed cell death 6 (PDCD6), a Ca 2+-binding protein, has been reported to be aberrantly expressed in all kinds of tumors. The aim of this study was to explore the role and mechanism of PDCD6 in hepatocellular carcinomas (HCCs).The expression levels of PDCD6 in liver cancer patients and HCC cell lines were analyzed using bioinformatics and Western blotting. Cell viability and metastasis were determined by methylthiazol tetrazolium (MTT) and transwell assays, respectively. And Western blotting was used to test related biomarkers and molecular pathway factors in HCC cell lines. LY294002, a PI3K inhibitor inhibiting AKT, was used to suppress the AKT/GSK3β/β-catenin pathway to help evaluate the role of this pathway in the HCC carcinogenesis associated with PDCD6.The analysis of The Cancer Genome Atlas Database suggested that high PDCD6 expression levels were relevant to liver cancer progression. This was consistent with our finding of higher levels of PDCD6 expression in HCC cell lines than in normal hepatocyte cell lines. The results of MTT, transwell migration, and Western blotting assays revealed that overexpression of PDCD6 positively regulated HCC cell proliferation, migration, and invasion. Conversely, the upregulation of PDCD6 expression in the presence of an AKT inhibitor inhibited HCC cell proliferation, migration, and invasion. In addition, PDCD6 promoted HCC cell migration and invasion by epithelial-mesenchymal transition. The mechanistic investigation proved that PDCD6 acted as a tumor promoter in HCC through the AKT/GSK3β/β-catenin pathway, increasing the expression of transcription factors and cellular proliferation and metastasis.PDCD6 has a tumor stimulative role in HCC mediated by AKT/GSK3β/β-catenin signaling and might be a potential target for HCC progression.Copyright © 2023 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.