Super-enhancer-associated INSM2 regulates lipid metabolism by modulating mTOR signaling pathway in neuroblastoma

Cao, Haibo; Zhuo, Ran; Zhang, Zimu; Wang, Jianwei; Tao, Yan-Fang; Yang, Randong; Guo, Xinyi; Chen, Yanling; Jia, Si-Qi; Yao, Ye; Yang, Pengcheng; Yu, Jinfang; Jiao, Wan-Yan; Li, Xiaolu; Fang, Fang; Xie, Yi; Li, Gen; Wu, Di; Wang, Hairong; Feng, Chen-Xi; Xu, Yunyun; Li, Zhiheng; Pan, Jian; Wang, Jian

doi:10.1186/s13578-022-00895-3

Cited by 4 publications

(2 citation statements)

References 66 publications

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“…Similarly, it was reported that ASF1B was significantly correlated with poor prognosis in several other cancer patients [ 31 , 32 ]. Cao H et al demonstrated that the upregulated expression of INSM2 promoted tumorigenesis and progression by regulating lipid metabolism in neuroblastoma and led to poor prognosis in neuroblastoma patients [ 33 ]. MT1B, known as an important isoform of metallothioneins (MTs), was reported to participate in the regulation of copper-zinc homeostasis, and MTs play an important role in tumorigenesis, angiogenesis, metastasis, proliferation and immunomodulation of cancers [ 34 ].…”

Section: Discussionmentioning

confidence: 99%

Comprehensive analysis of integrin αvβ3/α6β1 in prognosis and immune escape of prostate cancer

Liu,

He,

et al. 2023

Aging

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Integrin αvβ3/α6β1 are crucial in the transduction of intercellular cancer information, while their roles in prostate cancer (PCa) remain poorly understood. Here, we systematically analyzed the transcriptome, single nucleotide polymorphisms (SNPs) and clinical data of 495 PCa patients from the TCGA database and verified them in 220 GEO patients, and qPCR was used to validate the expression of the model genes in our patients. First, we found that integrin αvβ3/α6β1 was negatively correlated with most immune cell infiltration and immune functions and closely associated with poor survival in TCGA patients. Then, we divided these patients into two groups according to the expression level of αvβ3/α6β1, intersected differentially expressed genes of the two groups with the GEO dataset and identified eight biochemical recurrence-related genes (BRGs), and these genes were verified by qPCR in our patients. Next, these BRGs were used to construct a prognostic risk model by applying LASSO Cox regression. We found that the high-risk (HR) group showed poorer OS, PFS, biochemical recurrence and clinical characteristics than the low-risk (LR) group. In addition, the HR group was mainly enriched in the cell cycle pathway and had a higher TP53 mutation rate than the LR group. More importantly, lower immune cell infiltration and immune function, higher expression of PD-L1, PD-1, and CTLA4, and higher immune exclusion scores were identified in the HR group, suggesting a higher possibility of immune escape. These findings suggested the key role of integrin αvβ3/α6β1 in predicting prognosis, TP53 mutation and immune escape in PCa.

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Section: Discussionmentioning

confidence: 99%

Comprehensive analysis of integrin αvβ3/α6β1 in prognosis and immune escape of prostate cancer

Liu,

He,

et al. 2023

Aging

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“…Neuroblastoma (NB) is one of the most common neuroectodermal solid tumors in children [1,2]. It occurs in infancy and early childhood and is derived from primitive cells, mainly neural crest cells.…”

Section: Introductionmentioning

confidence: 99%

The BRD4 Inhibitor dBET57 Exerts Anticancer Effects by Targeting Superenhancer-Related Genes in Neuroblastoma

Jia

Zhuo

Zhang

et al. 2022

Journal of Immunology Research

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Neuroblastoma (NB) is the most common solid tumor of the neural crest cell origin in children and has a poor prognosis in high-risk patients. The oncogene MYCN was found to be amplified at extremely high levels in approximately 20% of neuroblastoma cases. In recent years, research on the targeted hydrolysis of BRD4 to indirectly inhibit the transcription of the MYCN created by proteolysis targeting chimaera (PROTAC) technology has become very popular. dBET57 (S0137, Selleck, TX, USA) is a novel and potent heterobifunctional small molecule degrader based on PROTAC technology. The purpose of this study was to investigate the therapeutic effect of dBET57 in NB and its potential mechanism. In this study, we found that dBET57 can target BRD4 ubiquitination and disrupt the proliferation ability of NB cells. At the same time, dBET57 can also induce apoptosis, cell cycle arrest, and decrease migration. Furthermore, dBET57 also has a strong antiproliferation function in xenograft tumor models in vivo. In terms of mechanism, dBET57 targets the BET protein family and the MYCN protein family by associating with CRBN and destroys the SE landscape of NB cells. Combined with RNA-seq and ChIP-seq public database analysis, we identified the superenhancer-related genes TBX3 and ZMYND8 in NB as potential downstream targets of dBET57 and experimentally verified that they play an important role in the occurrence and development of NB. In conclusion, these results suggest that dBET57 may be an effective new therapeutic drug for the treatment of NB.

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Metabolic reprogramming directed by super-enhancers in tumors: An emerging landscape

Zhou,

Li,

Ousmane

et al. 2024

Molecular Therapy

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Super-enhancer-associated INSM2 regulates lipid metabolism by modulating mTOR signaling pathway in neuroblastoma

Cited by 4 publications

References 66 publications

Comprehensive analysis of integrin αvβ3/α6β1 in prognosis and immune escape of prostate cancer

Comprehensive analysis of integrin αvβ3/α6β1 in prognosis and immune escape of prostate cancer

The BRD4 Inhibitor dBET57 Exerts Anticancer Effects by Targeting Superenhancer-Related Genes in Neuroblastoma

Metabolic reprogramming directed by super-enhancers in tumors: An emerging landscape

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