Super-enhancer-associated INSM2 regulates lipid metabolism by modulating mTOR signaling pathway in neuroblastoma
Abstract Background Abnormal lipid metabolism is one of the most prominent metabolic changes in cancer. Studies have shown that lipid metabolism also plays an important role in neuroblastoma. We recently discovered that the insulinoma-associated 2 gene (INSM2) could regulate lipid metabolism in neur...
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| Format: | Article |
| Language: | English |
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BMC
2022-09-01
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| Series: | Cell & Bioscience |
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| Online Access: | https://doi.org/10.1186/s13578-022-00895-3 |
| _version_ | 1828378008384176128 |
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| author | Haibo Cao Ran Zhuo Zimu Zhang Jianwei Wang Yanfang Tao Randong Yang Xinyi Guo Yanling Chen Siqi Jia Ye Yao Pengcheng Yang Juanjuan Yu Wanyan Jiao Xiaolu Li Fang Fang Yi Xie Gen Li Di Wu Hairong Wang Chenxi Feng Yunyun Xu Zhiheng Li Jian Pan Jian Wang |
| author_facet | Haibo Cao Ran Zhuo Zimu Zhang Jianwei Wang Yanfang Tao Randong Yang Xinyi Guo Yanling Chen Siqi Jia Ye Yao Pengcheng Yang Juanjuan Yu Wanyan Jiao Xiaolu Li Fang Fang Yi Xie Gen Li Di Wu Hairong Wang Chenxi Feng Yunyun Xu Zhiheng Li Jian Pan Jian Wang |
| author_sort | Haibo Cao |
| collection | DOAJ |
| description | Abstract Background Abnormal lipid metabolism is one of the most prominent metabolic changes in cancer. Studies have shown that lipid metabolism also plays an important role in neuroblastoma. We recently discovered that the insulinoma-associated 2 gene (INSM2) could regulate lipid metabolism in neuroblastoma (NB) and is improperly controlled by super enhancers, a mammalian genome region that has been shown to control the expression of NB cell identity genes. However, the specific molecular pathways by which INSM2 leads to NB disease development are unknown. Results We identified INSM2 as a gene regulated by super enhancers in NB. In addition, INSM2 expression levels were significantly upregulated in NB and correlated with poor prognosis in patients. We found that INSM2 drives the growth of NB cell lines both in vitro and in vivo. Knocking down INSM2 inhibited fatty acid metabolism in NB cells. Mechanistically, INSM2 regulates the expression of SREBP1 by regulating the mTOR signaling pathway, which in turn affects lipid metabolism, thereby mediating the occurrence and development of neuroblastoma. Conclusion INSM2 as a super-enhancer-associated gene could regulates lipid metabolism by modulating mTOR signaling pathway in neuroblastoma. |
| first_indexed | 2024-04-14T08:20:21Z |
| format | Article |
| id | doaj.art-b869f66dd9644849a66f1dcbf9e29e31 |
| institution | Directory Open Access Journal |
| issn | 2045-3701 |
| language | English |
| last_indexed | 2024-04-14T08:20:21Z |
| publishDate | 2022-09-01 |
| publisher | BMC |
| record_format | Article |
| series | Cell & Bioscience |
| spelling | doaj.art-b869f66dd9644849a66f1dcbf9e29e312022-12-22T02:04:14ZengBMCCell & Bioscience2045-37012022-09-0112111410.1186/s13578-022-00895-3Super-enhancer-associated INSM2 regulates lipid metabolism by modulating mTOR signaling pathway in neuroblastomaHaibo Cao0Ran Zhuo1Zimu Zhang2Jianwei Wang3Yanfang Tao4Randong Yang5Xinyi Guo6Yanling Chen7Siqi Jia8Ye Yao9Pengcheng Yang10Juanjuan Yu11Wanyan Jiao12Xiaolu Li13Fang Fang14Yi Xie15Gen Li16Di Wu17Hairong Wang18Chenxi Feng19Yunyun Xu20Zhiheng Li21Jian Pan22Jian Wang23Institute of Pediatric Research, Children’s Hospital of Soochow UniversityInstitute of Pediatric Research, Children’s Hospital of Soochow UniversityInstitute of Pediatric Research, Children’s Hospital of Soochow UniversityInstitute of Pediatric Research, Children’s Hospital of Soochow UniversityInstitute of Pediatric Research, Children’s Hospital of Soochow UniversityInstitute of Pediatric Research, Children’s Hospital of Soochow UniversityMedical College of Soochow UniversityInstitute of Pediatric Research, Children’s Hospital of Soochow UniversityInstitute of Pediatric Research, Children’s Hospital of Soochow UniversityInstitute of Pediatric Research, Children’s Hospital of Soochow UniversityInstitute of Pediatric Research, Children’s Hospital of Soochow UniversityInstitute of Pediatric Research, Children’s Hospital of Soochow UniversityInstitute of Pediatric Research, Children’s Hospital of Soochow UniversityInstitute of Pediatric Research, Children’s Hospital of Soochow UniversityInstitute of Pediatric Research, Children’s Hospital of Soochow UniversityInstitute of Pediatric Research, Children’s Hospital of Soochow UniversityInstitute of Pediatric Research, Children’s Hospital of Soochow UniversityInstitute of Pediatric Research, Children’s Hospital of Soochow UniversityInstitute of Pediatric Research, Children’s Hospital of Soochow UniversityInstitute of Pediatric Research, Children’s Hospital of Soochow UniversityInstitute of Pediatric Research, Children’s Hospital of Soochow UniversityInstitute of Pediatric Research, Children’s Hospital of Soochow UniversityInstitute of Pediatric Research, Children’s Hospital of Soochow UniversityInstitute of Pediatric Research, Children’s Hospital of Soochow UniversityAbstract Background Abnormal lipid metabolism is one of the most prominent metabolic changes in cancer. Studies have shown that lipid metabolism also plays an important role in neuroblastoma. We recently discovered that the insulinoma-associated 2 gene (INSM2) could regulate lipid metabolism in neuroblastoma (NB) and is improperly controlled by super enhancers, a mammalian genome region that has been shown to control the expression of NB cell identity genes. However, the specific molecular pathways by which INSM2 leads to NB disease development are unknown. Results We identified INSM2 as a gene regulated by super enhancers in NB. In addition, INSM2 expression levels were significantly upregulated in NB and correlated with poor prognosis in patients. We found that INSM2 drives the growth of NB cell lines both in vitro and in vivo. Knocking down INSM2 inhibited fatty acid metabolism in NB cells. Mechanistically, INSM2 regulates the expression of SREBP1 by regulating the mTOR signaling pathway, which in turn affects lipid metabolism, thereby mediating the occurrence and development of neuroblastoma. Conclusion INSM2 as a super-enhancer-associated gene could regulates lipid metabolism by modulating mTOR signaling pathway in neuroblastoma.https://doi.org/10.1186/s13578-022-00895-3Super-enhancerINSM2Lipid metabolismNeuroblastomamTORSREBP1 |
| spellingShingle | Haibo Cao Ran Zhuo Zimu Zhang Jianwei Wang Yanfang Tao Randong Yang Xinyi Guo Yanling Chen Siqi Jia Ye Yao Pengcheng Yang Juanjuan Yu Wanyan Jiao Xiaolu Li Fang Fang Yi Xie Gen Li Di Wu Hairong Wang Chenxi Feng Yunyun Xu Zhiheng Li Jian Pan Jian Wang Super-enhancer-associated INSM2 regulates lipid metabolism by modulating mTOR signaling pathway in neuroblastoma Cell & Bioscience Super-enhancer INSM2 Lipid metabolism Neuroblastoma mTOR SREBP1 |
| title | Super-enhancer-associated INSM2 regulates lipid metabolism by modulating mTOR signaling pathway in neuroblastoma |
| title_full | Super-enhancer-associated INSM2 regulates lipid metabolism by modulating mTOR signaling pathway in neuroblastoma |
| title_fullStr | Super-enhancer-associated INSM2 regulates lipid metabolism by modulating mTOR signaling pathway in neuroblastoma |
| title_full_unstemmed | Super-enhancer-associated INSM2 regulates lipid metabolism by modulating mTOR signaling pathway in neuroblastoma |
| title_short | Super-enhancer-associated INSM2 regulates lipid metabolism by modulating mTOR signaling pathway in neuroblastoma |
| title_sort | super enhancer associated insm2 regulates lipid metabolism by modulating mtor signaling pathway in neuroblastoma |
| topic | Super-enhancer INSM2 Lipid metabolism Neuroblastoma mTOR SREBP1 |
| url | https://doi.org/10.1186/s13578-022-00895-3 |
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