Super-enhancer-associated INSM2 regulates lipid metabolism by modulating mTOR signaling pathway in neuroblastoma
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Published:2022-09-16
Issue:1
Volume:12
Page:
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ISSN:2045-3701
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Container-title:Cell & Bioscience
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language:en
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Short-container-title:Cell Biosci
Author:
Cao Haibo, Zhuo Ran, Zhang Zimu, Wang Jianwei, Tao Yanfang, Yang Randong, Guo Xinyi, Chen Yanling, Jia Siqi, Yao Ye, Yang Pengcheng, Yu Juanjuan, Jiao Wanyan, Li Xiaolu, Fang Fang, Xie Yi, Li Gen, Wu Di, Wang Hairong, Feng Chenxi, Xu Yunyun, Li Zhiheng, Pan JianORCID, Wang Jian
Abstract
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.
Funder
Jiangsu Provincial Key Research and Development Program the Science and Technology Project of Soochow Suzhou Introduced Project of Clinical Medical Expert Team Suzhou Clinical Medical Center National Natural Science Foundation of China Science and Technology Support Program of Jiangsu Province
Publisher
Springer Science and Business Media LLC
Subject
General Biochemistry, Genetics and Molecular Biology
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