ZFP36 loss-mediated BARX1 stabilization promotes malignant phenotypes by transactivating master oncogenes in NSCLC
Abstract Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, with high morbidity and mortality worldwide. Although the dysregulation of BARX1 expression has been shown to be associated with malignant cancers, including NSCLC, the underlying mechanism remains elusive. In this s...
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| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2023-08-01
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| Series: | Cell Death and Disease |
| Online Access: | https://doi.org/10.1038/s41419-023-06044-z |
| _version_ | 1797740753391190016 |
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| author | Tongjia Zhang Lizhen Qiu Jiashun Cao Qiu Li Lifan Zhang Guoshun An Juhua Ni Hongti Jia Shuyan Li Kailong Li |
| author_facet | Tongjia Zhang Lizhen Qiu Jiashun Cao Qiu Li Lifan Zhang Guoshun An Juhua Ni Hongti Jia Shuyan Li Kailong Li |
| author_sort | Tongjia Zhang |
| collection | DOAJ |
| description | Abstract Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, with high morbidity and mortality worldwide. Although the dysregulation of BARX1 expression has been shown to be associated with malignant cancers, including NSCLC, the underlying mechanism remains elusive. In this study, we identified BARX1 as a common differentially expressed gene in lung squamous cell carcinoma and adenocarcinoma. Importantly, we uncovered a novel mechanism behind the regulation of BARX1, in which ZFP36 interacted with 3’UTR of BARX1 mRNA to mediate its destabilization. Loss of ZFP36 led to the upregulation of BARX1, which further promoted the proliferation, migration and invasion of NSCLC cells. In addition, the knockdown of BARX1 inhibited tumorigenicity in mouse xenograft. We demonstrated that BARX1 promoted the malignant phenotypes by transactivating a set of master oncogenes involved in the cell cycle, DNA synthesis and metastasis. Overall, our study provides insights into the mechanism of BARX1 actions in NSCLC and aids a better understanding of NSCLC pathogenesis. |
| first_indexed | 2024-03-12T14:16:57Z |
| format | Article |
| id | doaj.art-dba127c8f2274f2fb7e046c89c009018 |
| institution | Directory Open Access Journal |
| issn | 2041-4889 |
| language | English |
| last_indexed | 2024-03-12T14:16:57Z |
| publishDate | 2023-08-01 |
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| series | Cell Death and Disease |
| spelling | doaj.art-dba127c8f2274f2fb7e046c89c0090182023-08-20T11:22:23ZengNature Publishing GroupCell Death and Disease2041-48892023-08-0114811310.1038/s41419-023-06044-zZFP36 loss-mediated BARX1 stabilization promotes malignant phenotypes by transactivating master oncogenes in NSCLCTongjia Zhang0Lizhen Qiu1Jiashun Cao2Qiu Li3Lifan Zhang4Guoshun An5Juhua Ni6Hongti Jia7Shuyan Li8Kailong Li9Department of Biochemistry and Biophysics, Beijing Key Laboratory of Protein Posttranslational Modifications and Cell Function, School of Basic Medical Sciences, Peking University Health Science CenterDepartment of Biochemistry and Biophysics, Beijing Key Laboratory of Protein Posttranslational Modifications and Cell Function, School of Basic Medical Sciences, Peking University Health Science CenterDepartment of Thoracic Surgery, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua UniversityDepartment of Research, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua UniversityDepartment of Biochemistry and Biophysics, Beijing Key Laboratory of Protein Posttranslational Modifications and Cell Function, School of Basic Medical Sciences, Peking University Health Science CenterDepartment of Biochemistry and Biophysics, Beijing Key Laboratory of Protein Posttranslational Modifications and Cell Function, School of Basic Medical Sciences, Peking University Health Science CenterDepartment of Biochemistry and Biophysics, Beijing Key Laboratory of Protein Posttranslational Modifications and Cell Function, School of Basic Medical Sciences, Peking University Health Science CenterDepartment of Biochemistry and Biophysics, Beijing Key Laboratory of Protein Posttranslational Modifications and Cell Function, School of Basic Medical Sciences, Peking University Health Science CenterDepartment of Biochemistry and Biophysics, Beijing Key Laboratory of Protein Posttranslational Modifications and Cell Function, School of Basic Medical Sciences, Peking University Health Science CenterDepartment of Biochemistry and Biophysics, Beijing Key Laboratory of Protein Posttranslational Modifications and Cell Function, School of Basic Medical Sciences, Peking University Health Science CenterAbstract Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, with high morbidity and mortality worldwide. Although the dysregulation of BARX1 expression has been shown to be associated with malignant cancers, including NSCLC, the underlying mechanism remains elusive. In this study, we identified BARX1 as a common differentially expressed gene in lung squamous cell carcinoma and adenocarcinoma. Importantly, we uncovered a novel mechanism behind the regulation of BARX1, in which ZFP36 interacted with 3’UTR of BARX1 mRNA to mediate its destabilization. Loss of ZFP36 led to the upregulation of BARX1, which further promoted the proliferation, migration and invasion of NSCLC cells. In addition, the knockdown of BARX1 inhibited tumorigenicity in mouse xenograft. We demonstrated that BARX1 promoted the malignant phenotypes by transactivating a set of master oncogenes involved in the cell cycle, DNA synthesis and metastasis. Overall, our study provides insights into the mechanism of BARX1 actions in NSCLC and aids a better understanding of NSCLC pathogenesis.https://doi.org/10.1038/s41419-023-06044-z |
| spellingShingle | Tongjia Zhang Lizhen Qiu Jiashun Cao Qiu Li Lifan Zhang Guoshun An Juhua Ni Hongti Jia Shuyan Li Kailong Li ZFP36 loss-mediated BARX1 stabilization promotes malignant phenotypes by transactivating master oncogenes in NSCLC Cell Death and Disease |
| title | ZFP36 loss-mediated BARX1 stabilization promotes malignant phenotypes by transactivating master oncogenes in NSCLC |
| title_full | ZFP36 loss-mediated BARX1 stabilization promotes malignant phenotypes by transactivating master oncogenes in NSCLC |
| title_fullStr | ZFP36 loss-mediated BARX1 stabilization promotes malignant phenotypes by transactivating master oncogenes in NSCLC |
| title_full_unstemmed | ZFP36 loss-mediated BARX1 stabilization promotes malignant phenotypes by transactivating master oncogenes in NSCLC |
| title_short | ZFP36 loss-mediated BARX1 stabilization promotes malignant phenotypes by transactivating master oncogenes in NSCLC |
| title_sort | zfp36 loss mediated barx1 stabilization promotes malignant phenotypes by transactivating master oncogenes in nsclc |
| url | https://doi.org/10.1038/s41419-023-06044-z |
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