DDX24 通过调节非小细胞肺癌中的 RPL5 促进转移。

DDX24 promotes metastasis by regulating RPL5 in non-small cell lung cancer.

机构信息

Department of Interventional Medicine, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, P.R. China.

Guangdong Provincial Key Laboratory of Biomedical Imaging, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, P.R. China.

出版信息

Cancer Med. 2022 Dec;11(23):4513-4525. doi: 10.1002/cam4.4835. Epub 2022 Jul 21.

Abstract

PURPOSE

Non-small cell lung cancer (NSCLC) is a leading cause of cancer death, and metastasis is a crucial determinant of increased cancer mortality. DDX24 has garnered increased attention due to its correlation with tumorigenesis and malignant progression. However, the correlation between DDX24 and NSCLC remains unclear.

METHODS

DDX24 expression in NSCLC tissues and survival rate of patients was analyzed using bioinformatic analysis. Transwell assays, wound-healing assays, and tail vein lung colonization models were employed to determine the role of DDX24 in migration and invasion in vitro and in vivo. We searched for DDX24-interacting proteins using co-immunoprecipitation followed by mass spectroscopy and verified the interaction. The influence of DDX24 on RPL5 expression and ubiquitination was examined using protein stability assays.

RESULTS

DDX24 expression was upregulated in NSCLC cell lines and tumors of patients, particularly those with high tumor grades. A high DDX24 level was also correlated with a poor prognosis. DDX24 upregulation enhanced the migration and invasion ability of NSCLC cells, whereas its downregulation had the opposite effects. In vivo xenograft experiments confirmed that tumors with high DDX24 expression had higher metastatic abilities. The interaction between DDX24 and RPL5 promoted its ubiquitination and destabilized it.

CONCLUSIONS

DDX24 acted as a pro-tumorigenic factor and promoted metastasis in NSCLC. DDX24 interacted with RPL5 to promote its ubiquitination and degradation. As a result, targeting DDX24/RPL5 axis may provide a novel potential therapeutic strategy for NSCLC.

摘要

目的

非小细胞肺癌(NSCLC)是癌症死亡的主要原因,而转移是癌症死亡率增加的关键决定因素。DDX24 因其与肿瘤发生和恶性进展的相关性而受到越来越多的关注。然而,DDX24 与 NSCLC 之间的关系尚不清楚。

方法

通过生物信息学分析,分析 NSCLC 组织中 DDX24 的表达和患者的生存率。使用 Transwell 分析、划痕愈合分析和尾静脉肺定植模型,在体外和体内确定 DDX24 在迁移和侵袭中的作用。我们使用免疫共沉淀结合质谱法寻找 DDX24 的相互作用蛋白,并验证了相互作用。使用蛋白质稳定性测定法检查 DDX24 对 RPL5 表达和泛素化的影响。

结果

DDX24 在 NSCLC 细胞系和患者的肿瘤中表达上调,特别是那些肿瘤分级较高的患者。高水平的 DDX24 也与预后不良相关。DDX24 的上调增强了 NSCLC 细胞的迁移和侵袭能力,而下调则产生相反的效果。体内异种移植实验证实,表达高水平 DDX24 的肿瘤具有更高的转移能力。DDX24 和 RPL5 之间的相互作用促进了其泛素化和不稳定。

结论

DDX24 作为一种促肿瘤因子,促进 NSCLC 的转移。DDX24 与 RPL5 相互作用,促进其泛素化和降解。因此,靶向 DDX24/RPL5 轴可能为 NSCLC 提供一种新的潜在治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c131/9741967/db988c14b141/CAM4-11-4513-g006.jpg

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