Laboratory of Respiratory Diseases, the Affiliated Hospital of Guilin Medical University, Guilin, China.
Guangxi Key Laboratory of Molecular Medicine in Liver Injury and Repair, Guilin Medical University, Guilin, China.
J Cell Mol Med. 2020 Nov;24(22):13303-13313. doi: 10.1111/jcmm.15947. Epub 2020 Oct 5.
DEP domain containing 1(DEPDC1) is involved in the tumorigenesis of a variety of cancers. But its role in tumorigenesis of lung adenocarcinoma (LUAD) is not fully understood. Here, we investigated the role and the underlying mechanisms of DEPDC1 in the development of LUAD. The expression and prognostic values of DEPDC1 in LUAD were analysed by using the data from public databases. Gene enrichment in TCGA LUAD was analysed using GSEA software with the pre-defined gene sets. Cell proliferation, migration and invasion of A549 cells were examined with colony formation, Transwell and wound healing assays. The function of DEPDC1 in autophagy and RAS-ERK1/2 signalling was determined with Western blot assay upon DEPDC1 knockdown and/or overexpression in A549, HCC827 and H1993 cells. The results demonstrated that DEPDC1 expression was up-regulated in LUAD tissues, and its high expression was correlated with unfavourable prognosis. The data also showed that DEPDC1 knockdown impaired proliferation, migration and invasion of A549 cells. Most notably, the results showed that DEPDC1 up-regulated RAS expression and thus enhanced ERK1/2 activity, through which DEPDC1 could inhibit autophagy. In conclusion, our study revealed that DEPDC1 is up-regulated in LUAD tissues and plays an oncogenic role in LUAD, and that DEPDC1 inhibits autophagy through the RAS-ERK1/2 signalling in A549, HCC827 and H1993 cells.
DEP 结构域包含蛋白 1（DEPDC1）参与多种癌症的肿瘤发生。但其在肺腺癌（LUAD）肿瘤发生中的作用尚不完全清楚。在这里，我们研究了 DEPDC1 在 LUAD 发展中的作用及其潜在机制。通过使用公共数据库中的数据分析 LUAD 中 DEPDC1 的表达和预后价值。使用 GSEA 软件对 TCGA LUAD 中的基因富集进行分析，使用预定义的基因集。通过集落形成、Transwell 和划痕愈合实验检测 A549 细胞的增殖、迁移和侵袭。通过在 A549、HCC827 和 H1993 细胞中敲低和/或过表达 DEPDC1，用 Western blot 检测 DEPDC1 对自噬和 RAS-ERK1/2 信号的功能。结果表明，DEPDC1 在 LUAD 组织中表达上调，其高表达与不良预后相关。数据还表明，DEPDC1 敲低可损害 A549 细胞的增殖、迁移和侵袭。最值得注意的是，结果表明 DEPDC1 上调 RAS 表达，从而增强 ERK1/2 活性，通过这种方式 DEPDC1 可以抑制自噬。总之，我们的研究表明，DEPDC1 在 LUAD 组织中上调，并在 LUAD 中发挥致癌作用，并且 DEPDC1 通过 RAS-ERK1/2 信号在 A549、HCC827 和 H1993 细胞中抑制自噬。
