The crosstalk between SND1 and PDCD4 is associated with chemoresistance of non-small cell lung carcinoma cells

Abstract Lung cancer is the leading cause of cancer-related deaths worldwide. Non-small cell lung cancer (NSCLC) is highly resistant to chemo- or radiation therapy, which poses a huge challenge for treatment of advanced NSCLC. Previously, we demonstrated the oncogenic role of Tudor Staphylococcal nu...

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Main Authors: Yun Zhao, Shanel Dhani, Vladimir Gogvadze, Boris Zhivotovsky
Format: Article
Language:English
Published: Nature Publishing Group 2025-01-01
Series:Cell Death Discovery
Online Access:https://doi.org/10.1038/s41420-025-02310-5
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author Yun Zhao
Shanel Dhani
Vladimir Gogvadze
Boris Zhivotovsky
author_facet Yun Zhao
Shanel Dhani
Vladimir Gogvadze
Boris Zhivotovsky
author_sort Yun Zhao
collection DOAJ
description Abstract Lung cancer is the leading cause of cancer-related deaths worldwide. Non-small cell lung cancer (NSCLC) is highly resistant to chemo- or radiation therapy, which poses a huge challenge for treatment of advanced NSCLC. Previously, we demonstrated the oncogenic role of Tudor Staphylococcal nuclease (TSN, also known as Staphylococcal nuclease domain-containing protein 1, SND1), in regulating chemoresistance in NSCLC cells. Here, we showed that silencing of SND1 augmented the sensitivity of NSCLC cells to different chemotherapeutic drugs. Additionally, the expression of PDCD4 (a tumor suppressor highly associated with lung cancer) in NSCLC cells with low endogenous levels was attenuated by SND1 silencing, implying that SND1 might function as a molecular regulator upstream of PDCD4. PDCD4 is differentially expressed in various NSCLC cells. In the NSCLC cells (A549 and H23 cells) with low expression of PDCD4, despite the downregulation of PDCD4, silencing of SND1 still led to sensitization of NSCLC cells to treatment with different chemotherapeutic agents by the inhibition of autophagic activity. Thus, a novel correlation interlinking SND1 and PDCD4 in the regulation of NSCLC cells concerning chemotherapy was revealed, which contributes to understanding the mechanisms of chemoresistance in NSCLC.
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spelling doaj-art-14ed132fbf2b40e0bd658e5180e93a222025-02-02T12:08:47ZengNature Publishing GroupCell Death Discovery2058-77162025-01-0111111010.1038/s41420-025-02310-5The crosstalk between SND1 and PDCD4 is associated with chemoresistance of non-small cell lung carcinoma cellsYun Zhao0Shanel Dhani1Vladimir Gogvadze2Boris Zhivotovsky3Department of Occupational and Environmental Health, School of Public Health, Medical College of Soochow UniversityInstitute of Environmental Medicine, Karolinska InstitutetInstitute of Environmental Medicine, Karolinska InstitutetInstitute of Environmental Medicine, Karolinska InstitutetAbstract Lung cancer is the leading cause of cancer-related deaths worldwide. Non-small cell lung cancer (NSCLC) is highly resistant to chemo- or radiation therapy, which poses a huge challenge for treatment of advanced NSCLC. Previously, we demonstrated the oncogenic role of Tudor Staphylococcal nuclease (TSN, also known as Staphylococcal nuclease domain-containing protein 1, SND1), in regulating chemoresistance in NSCLC cells. Here, we showed that silencing of SND1 augmented the sensitivity of NSCLC cells to different chemotherapeutic drugs. Additionally, the expression of PDCD4 (a tumor suppressor highly associated with lung cancer) in NSCLC cells with low endogenous levels was attenuated by SND1 silencing, implying that SND1 might function as a molecular regulator upstream of PDCD4. PDCD4 is differentially expressed in various NSCLC cells. In the NSCLC cells (A549 and H23 cells) with low expression of PDCD4, despite the downregulation of PDCD4, silencing of SND1 still led to sensitization of NSCLC cells to treatment with different chemotherapeutic agents by the inhibition of autophagic activity. Thus, a novel correlation interlinking SND1 and PDCD4 in the regulation of NSCLC cells concerning chemotherapy was revealed, which contributes to understanding the mechanisms of chemoresistance in NSCLC.https://doi.org/10.1038/s41420-025-02310-5
spellingShingle Yun Zhao
Shanel Dhani
Vladimir Gogvadze
Boris Zhivotovsky
The crosstalk between SND1 and PDCD4 is associated with chemoresistance of non-small cell lung carcinoma cells
Cell Death Discovery
title The crosstalk between SND1 and PDCD4 is associated with chemoresistance of non-small cell lung carcinoma cells
title_full The crosstalk between SND1 and PDCD4 is associated with chemoresistance of non-small cell lung carcinoma cells
title_fullStr The crosstalk between SND1 and PDCD4 is associated with chemoresistance of non-small cell lung carcinoma cells
title_full_unstemmed The crosstalk between SND1 and PDCD4 is associated with chemoresistance of non-small cell lung carcinoma cells
title_short The crosstalk between SND1 and PDCD4 is associated with chemoresistance of non-small cell lung carcinoma cells
title_sort crosstalk between snd1 and pdcd4 is associated with chemoresistance of non small cell lung carcinoma cells
url https://doi.org/10.1038/s41420-025-02310-5
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