Department of General Medicine, Jiujiang City Key Laboratory of Cell Therapy, Jiujiang NO.1 People's Hospital, Jiujiang, China.
Department of Jiulong Community Health Service Centre, Jiujiang City Key Laboratory of Cell Therapy, Jiujiang NO.1 People's Hospital, Jiujiang, China.
Clin Respir J. 2024 Aug;18(8):e13824. doi: 10.1111/crj.13824.
Lung adenocarcinoma (LUAD) is a highly aggressive and rapidly fatal malignancy worldwide. Collagen XVII (COL17A1) has been implicated in various protumorigenic processes. However, the functions and mechanisms of COL17A1 in LUAD progression still remain elusive.
COL17A1 and ubiquitin-specific protease 22 (USP22) mRNA analysis was performed by quantitative PCR, and their protein levels were detected by immunoblotting and immunohistochemistry. The functional influence was evaluated by determining cell viability, proliferation, apoptosis, invasion, migration, and ferroptosis in vitro, as well as xenograft growth in vivo. Co-immunoprecipitation (Co-IP) and IP experiments were used to examine the USP22/COL17A1 interaction and COL17A1 deubiquitination. Cycloheximide treatment was used to analyze COL17A1 protein stability.
COL17A1 and USP22 were upregulated in human LUAD tissues and cell lines. Functionally, COL17A1 knockdown acted for the suppression of LUAD cell growth, invasion, and migration as well as promotion of cell apoptosis and ferroptosis in vitro. COL17A1 knockdown could diminish the tumorigenicity of LUAD cells in vivo. Mechanistically, USP22 stabilized and upregulated COL17A1 by enhancing the deubiquitination of COL17A1. Additionally, reexpression of COL17A1 could reverse USP22 silencing-induced phenotype changes of LUAD cells in vitro.
Our findings demonstrate that USP22-stabilized COL17A1 possesses oncogenic activity in LUAD. We propose that USP22 and COL17A1 would be potential targets for the establishment of therapeutic approaches against LUAD.
肺腺癌（LUAD）是一种在全球范围内具有高度侵袭性和快速致命性的恶性肿瘤。COL17A1（XVII 型胶原）已被牵涉到各种促进肿瘤发生的过程中。然而，COL17A1 在 LUAD 进展中的功能和机制仍不清楚。
通过定量 PCR 分析 COL17A1 和泛素特异性蛋白酶 22（USP22）的 mRNA 水平，并通过免疫印迹和免疫组织化学检测其蛋白水平。通过测定体外细胞活力、增殖、凋亡、侵袭、迁移和铁死亡，以及体内异种移植生长，评估功能影响。使用共免疫沉淀（Co-IP）和免疫沉淀（IP）实验来检测 USP22/COL17A1 相互作用和 COL17A1 的去泛素化。使用环己酰亚胺处理来分析 COL17A1 蛋白稳定性。
COL17A1 和 USP22 在人 LUAD 组织和细胞系中上调。功能上，COL17A1 敲低可抑制 LUAD 细胞生长、侵袭和迁移，并促进体外细胞凋亡和铁死亡。COL17A1 敲低可减少 LUAD 细胞在体内的致瘤性。机制上，USP22 通过增强 COL17A1 的去泛素化来稳定和上调 COL17A1。此外，COL17A1 的再表达可逆转 USP22 沉默诱导的 LUAD 细胞体外表型变化。
我们的研究结果表明，USP22 稳定的 COL17A1 在 LUAD 中具有致癌活性。我们提出 USP22 和 COL17A1 可能是针对 LUAD 建立治疗方法的潜在靶点。
