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沉默 UCHL3 通过抑制 DNA 修复增强非小细胞肺癌细胞的放射敏感性。

Silencing UCHL3 enhances radio-sensitivity of non-small cell lung cancer cells by inhibiting DNA repair.

机构信息

Department of Oncology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People's Republic of China.

Department of Hemodialysis, Nanchang First Hospital, Nanchang, Jiangxi, People's Republic of China.

出版信息

Aging (Albany NY). 2021 May 19;13(10):14277-14288. doi: 10.18632/aging.203043.

DOI:10.18632/aging.203043
PMID:34016790
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8202860/
Abstract

UCHL3 belongs to the UCH family and is involved in multiple biological processes. However, the biological functions and underlying mechanisms of action of UCHL3 in radio-sensitivity of non-small cell lung cancer (NSCLC) remain unknown. Here, we reported that the expression of UCHL3 was significantly up-regulated in NSCLC tissues and cell lines, and associated with poor prognosis of NSCLC patients. The expression of UCHL3 of NSCLC cells was increased after exposure to ionizing radiation (IR). Moreover, we found that knockdown of UCHL3 enhanced the radio-sensitivity of NSCLC cells both and . Furthermore, γH2AX foci staining and Western blot analysis showed that knockdown of UCHL3 increased IR-induced DNA damage. Knockdown of UCHL3 in NSCLC cells decreased homologous recombination (HR) repair efficiency and RAD51 foci formation. Collectively, our study revealed that knockdown of UCHL3 enhanced the radio-sensitivity of NSCLC cells and increased IR-induced DNA damage via impairing HR repair.

摘要

UCHL3 属于 UCH 家族，参与多种生物学过程。然而，UCHL3 在非小细胞肺癌（NSCLC）放射敏感性中的生物学功能和作用机制尚不清楚。在这里，我们报道 UCHL3 在 NSCLC 组织和细胞系中表达显著上调，并与 NSCLC 患者的不良预后相关。暴露于电离辐射（IR）后，NSCLC 细胞中 UCHL3 的表达增加。此外，我们发现 UCHL3 的敲低增强了 NSCLC 细胞的放射敏感性。进一步的γH2AX 焦点染色和 Western blot 分析表明，UCHL3 的敲低增加了 IR 诱导的 DNA 损伤。在 NSCLC 细胞中敲低 UCHL3 降低了同源重组（HR）修复效率和 RAD51 焦点形成。总之，我们的研究表明，敲低 UCHL3 通过损害 HR 修复增强了 NSCLC 细胞的放射敏感性，并增加了 IR 诱导的 DNA 损伤。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81a5/8202860/42766bfd1e89/aging-13-203043-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81a5/8202860/80c5135bd87a/aging-13-203043-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81a5/8202860/154e48e66b91/aging-13-203043-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81a5/8202860/2968c8915cd9/aging-13-203043-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81a5/8202860/bd910f19e963/aging-13-203043-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81a5/8202860/42766bfd1e89/aging-13-203043-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81a5/8202860/80c5135bd87a/aging-13-203043-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81a5/8202860/154e48e66b91/aging-13-203043-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81a5/8202860/2968c8915cd9/aging-13-203043-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81a5/8202860/bd910f19e963/aging-13-203043-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81a5/8202860/42766bfd1e89/aging-13-203043-g005.jpg

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