Synergistic effect of PAF inhibition and X-ray irradiation in non-small cell lung cancer cells
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ORIGINAL ARTICLE
Synergistic effect of PAF inhibition and X-ray irradiation in non-small cell lung cancer cells Yamei Chen1 · Ying Jin1,2 · Hangjie Ying1 · Peng Zhang1 · Ming Chen1,3 · Xiao Hu1,3 Received: 21 June 2020 / Accepted: 23 October 2020 © Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Purpose Proliferating cell nuclear antigen-associated factor (PAF) is involved in cancer cell growth and associated with cell death induced by ultraviolet (UV) radiation. However, the contribution of PAF to radiotherapy sensitivity in non-small cell lung cancer (NSCLC) is unknown. The aim of this study was to investigate the relationship between PAF expression and radiotherapy response in NSCLC. Methods Associations between PAF expression and patient survival outcomes were evaluated using publicly available online gene expression datasets. RNA interference was performed to knockdown PAF expression in the NSCLC cells. The effects of PAF knockdown on cell proliferation, migration, apoptosis, DNA damage, and activation of MEK/ERK and Wnt/β-catenin signaling pathways following X-ray irradiation were evaluated in vitro. Results PAF was found to be overexpressed in lung cancer tissues compared with normal samples, and elevated PAF expression was significantly correlated with inferior patient survival. In vitro, knockdown of PAF inhibited cell proliferation, cell apoptosis, and migration induced by X-ray irradiation. Moreover, X-ray-induced intracellular DNA strand damage was more obvious following PAF knockdown. Additionally, PAF knockdown inhibited activation of the MEK/ERK and Wnt/β-catenin signaling pathways in X-ray-irradiated A549 cells. Conclusion These data demonstrate that reduced expression of PAF enhances radiosensitivity in NSCLC cells. Mechanistically, inhibition of the MEK/ERK and Wnt/β-catenin signaling pathways caused by PAF interference may lead to impaired cell function and enhance sensitivity to X-rays. Targeting PAF may therefore serve as a potential therapeutic strategy to increase the efficiency of radiotherapy in NSCLC patients, ultimately improving patient survival.
Keywords Proliferating cell nuclear antigen-associated factor · KIAA0101 · Radiosensitivity · Lung cancer · Lung adenocarcinoma
Introduction Lung cancer (LC) is one of the most common cancer types and accounts for the highest cancer mortality worldwide
[1, 2]. Non-small cell lung cancer (NSCLC) accounts for approximately 80% of all LC cases, and more than 60% of patients are diagnosed with advanced or metastatic disease (stage III or IV) [3]. The most common histological type
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00066-020-01708-7) contains supplementary material, which is available to authorized users. Dr. Ming Chen
2
Department of Medical Oncology, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, 310022 Hangzhou, Zhejiang, China
3
Depa
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