OTU deubiquitinase 5 inhibits the progression of non-small cell lung cancer via regulating p53 and PDCD5.,Chemical Biology & Drug Design

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OTU deubiquitinase 5 inhibits the progression of non-small cell lung cancer via regulating p53 and PDCD5.
Chemical Biology & Drug Design ( IF 3.2 ) Pub Date : 2020-04-04 , DOI: 10.1111/cbdd.13688
Xiao-Yun Kang _{1,

2} , Jing Zhang ₁ , Ling Tang ₁ , Liu Huang ₁ , Jin Tong ₃ , Qiang Fu ₁

Affiliation

Non‐small cell lung cancer (NSCLC) has the highest morbidity and mortality worldwide. OTU deubiquitinase 5 (OTUD5), a deubiquitinating enzyme, can enhance the stability of p53 and programmed cell death 5 (PDCD5), a protein related to the apoptosis, by deubiquitination. This study aimed to explore the biological function and underlying mechanism of OTUD5 in NSCLC. Western blot and qRT‐PCR were used to detect the expression of OTUD5 protein and mRNA in NSCLC tissues and cells, respectively. RNAi was adopted to construct an OTUD5 low‐expression model while the plasmids overexpressing p53 and PDCD5 were used to establish the overexpression models, respectively. CCK‐8 assay, transwell assay, and apoptosis assay were carried out to analyze the changes in the proliferation, migration, and chemoresistance of A549 and HCC827 cells. The mechanism of OTUD5 in NSCLC was studied by Western blot. Down‐regulated OTUD5 in NSCLC tissues was significantly correlated to a poor prognosis. The knockdown of OTUD5 inactivated p53 and PDCD5, promoting the proliferation and metastasis of NSCLC cells while inhibiting their apoptosis. OTUD5 knockdown also enhanced the resistance of NSCLC cells to doxorubicin and cisplatin. OTUD5 acted as a tumor suppressor in NSCLC by regulating the p53 and PDCD5 pathways.

中文翻译：

OTU去泛素酶5通过调节p53和PDCD5抑制非小细胞肺癌的发展。

非小细胞肺癌（NSCLC）的发病率和死亡率是全球最高的。OTU去泛素化酶5（OTUD5）是一种去泛素化酶，可通过去泛素化作用来增强p53的稳定性和程序性细胞死亡5（PDCD5）（一种与细胞凋亡相关的蛋白质）。本研究旨在探讨OTUD5在NSCLC中的生物学功能及其潜在机制。Western blot和qRT-PCR分别检测OTUD5蛋白和mRNA在NSCLC组织和细胞中的表达。RNAi被用来构建OTUD5低表达模型，而质粒p53和PDCD5则被过度表达。进行CCK-8测定，transwell测定和凋亡测定以分析A549和HCC827细胞的增殖，迁移和化学抗性的变化。Western blot研究了OTUD5在NSCLC中的作用机制。NSCLC组织中OTUD5的下调与不良预后显着相关。敲除OTUD5可灭活p53和PDCD5，从而促进NSCLC细胞的增殖和转移，同时抑制其凋亡。OTUD5敲低还增强了NSCLC细胞对阿霉素和顺铂的耐药性。OTUD5通过调节p53和PDCD5途径在NSCLC中起肿瘤抑制作用。

更新日期：2020-04-04

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