SOX1 Functions as a Tumor Suppressor by Repressing HES1 in Lung Cancer
The development of lung cancer is a complex process that involves many genetic and epigenetic changes. Sex-determining region Y (SRY)-box (SOX) genes encode a family of proteins that are involved in the regulation of embryonic development and cell fate determination. SOX1 is hypermethylated in human...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-04-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/15/8/2207 |
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| author | Shan-Yueh Chang Ti-Hui Wu Yu-Lueng Shih Ying-Chieh Chen Her-Young Su Chih-Feng Chian Ya-Wen Lin |
| author_facet | Shan-Yueh Chang Ti-Hui Wu Yu-Lueng Shih Ying-Chieh Chen Her-Young Su Chih-Feng Chian Ya-Wen Lin |
| author_sort | Shan-Yueh Chang |
| collection | DOAJ |
| description | The development of lung cancer is a complex process that involves many genetic and epigenetic changes. Sex-determining region Y (SRY)-box (SOX) genes encode a family of proteins that are involved in the regulation of embryonic development and cell fate determination. SOX1 is hypermethylated in human cancers. However, the role of SOX1 in the development of lung cancer is unclear. We used quantitative methylation-specific polymerase chain reaction (MSP), quantitative reverse transcription polymerase chain reaction (RT–PCR) analysis, and web tools to confirm the frequent epigenetic silencing of SOX1 in lung cancer. Stable overexpression of SOX1 repressed cell proliferation, anchorage-independent growth, and invasion in vitro as well as cancer growth and metastasis in a xenograft mouse model. Knockdown of SOX1 by the withdrawal of doxycycline partly restored the malignant phenotype of inducible SOX1-expressing NSCLC cells. Next, we discovered the potential downstream pathways of SOX1 using RNA-seq analysis and identified HES1 as a direct target of SOX1 using chromatin immunoprecipitation (ChIP)-PCR. Furthermore, we performed phenotypic rescue experiments to prove that overexpression of HES1-FLAG in SOX1-expressing H1299 cells partly reversed the tumor-suppressive effect. Taken together, these data demonstrated that SOX1 acts as a tumor suppressor by directly inhibiting HES1 during the development of NSCLC. |
| first_indexed | 2024-03-11T05:10:36Z |
| format | Article |
| id | doaj.art-f361675a13464f6a98380a21f64d5f12 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-11T05:10:36Z |
| publishDate | 2023-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-f361675a13464f6a98380a21f64d5f122023-11-17T18:37:50ZengMDPI AGCancers2072-66942023-04-01158220710.3390/cancers15082207SOX1 Functions as a Tumor Suppressor by Repressing HES1 in Lung CancerShan-Yueh Chang0Ti-Hui Wu1Yu-Lueng Shih2Ying-Chieh Chen3Her-Young Su4Chih-Feng Chian5Ya-Wen Lin6Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei 11490, TaiwanDivision of Thoracic Surgery, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei 11490, TaiwanDivision of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei 11490, TaiwanDivision of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei 11490, TaiwanGraduate Institute of Medical Sciences, National Defense Medical Center, Taipei 11490, TaiwanDivision of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei 11490, TaiwanGraduate Institute of Medical Sciences, National Defense Medical Center, Taipei 11490, TaiwanThe development of lung cancer is a complex process that involves many genetic and epigenetic changes. Sex-determining region Y (SRY)-box (SOX) genes encode a family of proteins that are involved in the regulation of embryonic development and cell fate determination. SOX1 is hypermethylated in human cancers. However, the role of SOX1 in the development of lung cancer is unclear. We used quantitative methylation-specific polymerase chain reaction (MSP), quantitative reverse transcription polymerase chain reaction (RT–PCR) analysis, and web tools to confirm the frequent epigenetic silencing of SOX1 in lung cancer. Stable overexpression of SOX1 repressed cell proliferation, anchorage-independent growth, and invasion in vitro as well as cancer growth and metastasis in a xenograft mouse model. Knockdown of SOX1 by the withdrawal of doxycycline partly restored the malignant phenotype of inducible SOX1-expressing NSCLC cells. Next, we discovered the potential downstream pathways of SOX1 using RNA-seq analysis and identified HES1 as a direct target of SOX1 using chromatin immunoprecipitation (ChIP)-PCR. Furthermore, we performed phenotypic rescue experiments to prove that overexpression of HES1-FLAG in SOX1-expressing H1299 cells partly reversed the tumor-suppressive effect. Taken together, these data demonstrated that SOX1 acts as a tumor suppressor by directly inhibiting HES1 during the development of NSCLC.https://www.mdpi.com/2072-6694/15/8/2207SOX1tumor suppressorlung cancerHES1 |
| spellingShingle | Shan-Yueh Chang Ti-Hui Wu Yu-Lueng Shih Ying-Chieh Chen Her-Young Su Chih-Feng Chian Ya-Wen Lin SOX1 Functions as a Tumor Suppressor by Repressing HES1 in Lung Cancer Cancers SOX1 tumor suppressor lung cancer HES1 |
| title | SOX1 Functions as a Tumor Suppressor by Repressing HES1 in Lung Cancer |
| title_full | SOX1 Functions as a Tumor Suppressor by Repressing HES1 in Lung Cancer |
| title_fullStr | SOX1 Functions as a Tumor Suppressor by Repressing HES1 in Lung Cancer |
| title_full_unstemmed | SOX1 Functions as a Tumor Suppressor by Repressing HES1 in Lung Cancer |
| title_short | SOX1 Functions as a Tumor Suppressor by Repressing HES1 in Lung Cancer |
| title_sort | sox1 functions as a tumor suppressor by repressing hes1 in lung cancer |
| topic | SOX1 tumor suppressor lung cancer HES1 |
| url | https://www.mdpi.com/2072-6694/15/8/2207 |
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