Super-enhancer-associated INSM2 Regulates Lipid Metabolism by Modulating MTOR Signaling Pathway in Neuroblastoma

Overview

Journal Cell Biosci

Publisher Biomed Central

Specialty Biology

Date 2022 Sep 16

PMID 36114560

Authors

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

Affiliations

Soon will be listed here.

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.

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