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super enhancers:Pathogenic roles and potential therapeutic targets for acute myeloid leukemia(AML)

Genes & Diseases 2022年第6期9卷 1466-1477页

作者： Ziyang Cao Yi Shu Jinxia Wang Chunxia Wang Tienan Feng Li Yang Jingbo Shao Lin Zou Clinical Research Unit Shanghai Children’s HospitalShanghai Jiao Tong UniversityShanghai 200062PR China Institute of Pediatric Infection ImmunityCritical Care MedicineShanghai Jiao Tong University School of MedicineShanghai 200062PR China Center for Clinical Molecular Laboratory Medicine of Children’s Hospital of Chongqing Medical University Chongqing 400014PR China Clinical Research Institute Shanghai Jiao Tong University School of MedicineShanghai 200025PR China Department of Hematology The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016PR China Department of Hematology/Oncology Shanghai Children’s HospitalShanghai Jiao Tong UniversityShanghai 200062PR China

Acute myeloid leukemia(AML)is a malignant hematological tumor with disordered oncogenes/tumor suppressor genes and limited treatments.The potent anti-cancer effects of bromodomain and extra-terminal domain(BET)inhibitors,targeting the key component of super enhancers,in early clinical trials on AML patients,implies the critical role of super enhancers in AML.Here,we review the concept and characteristic of super enhancer,and then summarize the current researches about super enhancers in AML pathogenesis,diagnosis and classification,followed by illustrate the potential super enhancer-related targets and drugs,and propose the future directions of super enhancers in AML.This information provides integrated insight into the roles of super enhancers in this disease.

关键词： Classification Leukemogenesis super enhancer Therapy targets

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FOSL1 Promotes Malignant Progression of Head and Neck Squamous Cell Carcinoma through super-enhancer-Driven Transcription Program

FOSL1 Promotes Malignant Progression of Head and Neck Squamo...

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2020年全国口腔颌面-头颈肿瘤学术大会暨中华口腔医学...

作者：王成中山大学光华口腔医学院附属口腔医院

Purpose/Background:FOSL1, an AP1 family member, has been reported to promote oncogenesis of head and neck squamous cell carcinoma(HNSCC). However, the molecular mechanisms of FOSL1 in maintaining cancer stemness and p... 详细信息

关键词： Head and neck squamous cell carcinoma super enhancer FOSL1 Metastasis

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super-enhancers drive the core transcriptional regulatory circuitry to regulate abiraterone resistance in castration-resistant prostate cancer

Super-enhancers drive the core transcriptional regulatory ci...

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2021年中国肿瘤标志物学术大会暨第十五届肿瘤标志物青...

作者： Jiamin Wang Xianping Shi School of Basic Medicine Guangzhou Medical University

Objective: Prostate cancer is the most common malignancy of male genitourinary system. Castration refractory prostate cancer(CRPC) is the leading cause of cancer-related death in men in the United States. Due to the relative lack of treatment options, almost all patients with CRPC eventually develop androgen treatment-resistant CRPC as the disease progresses. The potential mechanism of androgen therapy resistance to CRPC is still unknown. Therefore, it is vital to identify new carcinogenic pathways for the treatment of androgen treatment-resistant CRPC, and more efficient drugs are urgently needed because of the lack of valid chemotherapies that can provide satisfactory clinical outcomes for androgen treatment-resistant CRPC patients.super-enhancers(SEs) are large clusters of transcriptional enhancers, including populations of transcription factors(TFs), cofactors, chromatin regulators, and transcription apparatus occupying super-enhancers,which drive the expression of genes that define cell identity. Tumor cells assemble their own specific SEs to form a core transcriptional regulation circuits(CRCs), which significantly promotes the expression of multiple oncogenes, thereby enhances the ability of tumor cell proliferation, invasion and metastasis.In this study, by comparing the transcription profiles of super enhancers in abiraterone-resistant/sensitive CRPC cell lines, the key role of specific super enhancers in the regulation of CRCs during the development of abiraterone-resistant CRPC was explored, providing guidance for the delay of the development of abiraterone-resistant CRPC and clinical target therapy.Methods: super enhancer regulatory profiles and transcriptional expression levels of abiraterone resistant/sensitive cell lines and tumor specimens were obtained by chromatin immunoprecipitation sequencing(ChIP-seq) and RNA sequencing(RNA-seq), and transcriptional factor regulatory profiles were obtained by TF ChIP sequencing. Through "ROSE", "CRCapper" and other bioinformatics analysis, the possibility com

关键词： CRPC Abiraterone super enhancer Core transcriptional regulation circuits CRC

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