Department of Critical Medicine, Weifang People's Hospital, Weifang, China.
Department of Chinese Medicine, Weifang People's Hospital, Weifang, China.
Thorac Cancer. 2022 Mar;13(5):761-770. doi: 10.1111/1759-7714.14320. Epub 2022 Jan 30.
Lung cancer results in the highest mortality associated with cancer worldwide. Non-small cell cancer (NSCLC) is the leading subtype of lung cancer. Ovarian tumor protease (OTU) domain-containing protein 1 (OTUD1) is a member of the OTU subfamily of DUBs, and its function in NSCLC remains unclear.
GEPIA database was employed to reveal the expression level of OTUD1 in addition to Krüppel- like factor 4 (KLF4) in NSCLC tissue samples and prove the correlation between OTUD1 and KLF4. The protein level was estimated using western blot. Cell counting kit-8 (CCK-8) assay was used to detect cell viability and transwell assay was utilized to observe cell migration and invasion. Cycloheximide (CHX) was introduced to measure half-lives of KLF4 and deubiquitination assay was used to detect deubiquitination ability of OTUD1.
OTUD1 expression was downregulated in NSCLC tissues and cells. Overexpression of OTUD1 inhibited NSCLC cell progression and it was promoted by knockdown of OTUD1. OTUD1 was positively correlated with KLF4 and stabilized KLF4 at protein level by deubiquitinating KLF4. Overexpressing KLF4 dramatically eliminated the effects of OTUD1 on the development of NSCLC cells.
Our study revealed that OTUD1 suppresses NSCLC progression by mediating KLF4 stabilization, which suggests a potential gene target for the future treatment of NSCLC.
肺癌是全球癌症相关死亡率最高的疾病。非小细胞癌（NSCLC）是肺癌的主要亚型。卵巢肿瘤蛋白酶（OTU）结构域包含蛋白 1（OTUD1）是 DUBs 家族 OTU 亚家族的成员，其在 NSCLC 中的功能尚不清楚。
使用 GEPIA 数据库揭示 NSCLC 组织样本中 OTUD1 与 Kruppel 样因子 4（KLF4）的表达水平，并证明 OTUD1 与 KLF4 之间的相关性。使用蛋白质印迹法估计蛋白水平。使用细胞计数试剂盒-8（CCK-8）测定法检测细胞活力，使用 Transwell 测定法观察细胞迁移和侵袭。引入环已酰亚胺（CHX）测量 KLF4 的半衰期，并使用去泛素化测定法检测 OTUD1 的去泛素化能力。
OTUD1 在 NSCLC 组织和细胞中表达下调。OTUD1 的过表达抑制了 NSCLC 细胞的进展，而 OTUD1 的敲低则促进了 NSCLC 细胞的进展。OTUD1 与 KLF4 呈正相关，并通过去泛素化 KLF4 稳定 KLF4 蛋白水平。过表达 KLF4 显著消除了 OTUD1 对 NSCLC 细胞发育的影响。
我们的研究表明，OTUD1 通过介导 KLF4 的稳定来抑制 NSCLC 的进展，这为 NSCLC 的未来治疗提供了一个潜在的基因靶点。
