A5101515541- Protein Degradation and Inhibitors
- Ubiquitin and proteasome pathways
- Neuroblastoma Research and Treatments
- Multiple Myeloma Research and Treatments
- Histone Deacetylase Inhibitors Research
- Acute Myeloid Leukemia Research
- CAR-T cell therapy research
- Cancer, Hypoxia, and Metabolism
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Peptidase Inhibition and Analysis
- Toxin Mechanisms and Immunotoxins
- Genomics, phytochemicals, and oxidative stress
- Autoimmune and Inflammatory Disorders Research
- Bioactive Compounds and Antitumor Agents
- Phosphodiesterase function and regulation
- RNA Interference and Gene Delivery
- RNA Research and Splicing
- RNA modifications and cancer
- Lung Cancer Research Studies
- Genetics and Neurodevelopmental Disorders
- interferon and immune responses
- Mast cells and histamine
- RNA regulation and disease
- Microtubule and mitosis dynamics
- Natural Compounds in Disease Treatment
Soochow University
2021-2024
Children's Hospital of Suzhou University
2022
Wenzhou Medical University
2022
Soochow University
2021
Acute myeloid leukemia (AML) is a highly cancerous and aggressive hematologic disease with elevated levels of drug resistance relapse resulting in high mortality. Recently, bromodomains extra-terminal (BET) protein inhibitors have been extensively researched hematological tumors as potential anticancer agents. MZ1 novel BET inhibitor that mediates selective proteins degradation suppression tumor growth through proteolysis-targeting chimeras (PROTAC) technology. Accordingly, this study aimed...
Objective Suppression of bromodomain and extra terminal (BET) proteins has a bright prospect to treat MYC-driven tumors. Bromodomain containing 4 (BRD4) is one the BET proteins. ARV-825, consisting BRD4 inhibitor conjugated with cereblon ligand using proteolysis-targeting chimera (PROTAC) technology, was proven decrease tumor growth effectively continuously. Nevertheless, efficacy mechanisms ARV-825 in gastric cancer are still poorly understood. Methods Cell counting kit 8 assay, lentivirus...
Acute myeloid leukemia (AML) represents an aggressive hematopoietic malignancy with a prognosis inferior to that of other leukemias. Recent targeted therapies offer new opportunities achieve better treatment outcomes. However, due the complex heterogeneity AML, its remains dismal. In this study, we first identified correlation between high expression BRD4 and overall survival patients AML. Targeted degradation BRD2, BRD3, proteins by dBET1, proteolysis-targeting chimera (PROTAC) against...
Neuroblastoma (NB) is a common extracranial malignancy with high mortality in children. Recently, super-enhancers (SEs) have been reported to play critical role the tumorigenesis and development of NB via regulating wide range oncogenes Thus, synthesis identification chemical inhibitors specifically targeting SEs are great urgency for clinical therapy NB. This study aimed characterize activity inhibitor GNE987, which targets BRD4, In this study, we found that nanomolar concentrations GNE987...
Abstract Background Acute myeloid leukemia (AML) is a malignancy of the hematopoietic system, and childhood AML accounts for about 20% pediatric leukemia. ANP32B, an important nuclear protein associated with proliferation, has been found to regulate hematopoiesis CML leukemogenesis by inhibiting p53 activity. However, recent study suggests that ANP32B exerts suppressive effect on B-cell acute lymphoblastic (ALL) in mice activating PU.1. Nevertheless, precise underlying mechanism remains...
Super enhancers (SEs) are genomic regions comprising multiple closely spaced enhancers, typically occupied by a high density of cell-type-specific master transcription factors (TFs) and frequently enriched in key oncogenes various tumors, including neuroblastoma (NB), one the most prevalent malignant solid tumors children originating from neural crest. Cyclin-dependent kinase 5 regulatory subunit-associated protein 3 (CDK5RAP3) is newly identified super-enhancer-driven gene regulated TFs NB;...
Abstract Background Super-enhancers (SEs) typically govern the expression of critical oncogenes and play a fundamental role in initiation progression cancer. Focusing on genes that are abnormally regulated by SE cancer may be new strategy for understanding pathogenesis. In context this investigation, we have identified previously unreported SE-driven gene IRF2BP2 neuroblastoma (NB). Methods The prognostic value were detected public databases clinical samples. effect NB cell growth apoptosis...
Abstract Recent studies uncovered the emerging roles of SAPCD2 (suppressor anaphase-promoting complex domain containing 2) in several types human cancer. However, functions and underlying mechanisms progression neuroblastoma (NB) remain elusive. Herein, through integrative analysis public datasets regulatory network GSK-J4, a small-molecule drug with anti-NB activity, we identified as an appealing target high connection to poor prognosis NB. promoted NB vitro vivo. Mechanistically, could...
AML (acute myeloid leukemia) is a common hematological malignancy in children with poor treatment effects and prognosis. Recent studies have shown that as novel BRD4 (bromodomain containing 4) PROTACs (proteolysis targeting chimeras) degrader, GNE-987 can slow down the growth of various tumors increase apoptosis, promising clinical prospects. However, function molecular mechanism remain unclear. This study aimed at investigating therapeutic effect on its underlying mechanism. The association...
Abstract T-cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive hematologic malignancy originating from T progenitor cells. It accounts for 15% of childhood and 25% adult ALL cases. GNE-987 novel chimeric molecule developed using proteolysis-targeting chimeras (PROTAC) technology targeted therapy. consists potent inhibitor the bromodomain extraterminal (BET) protein, as well E3 ubiquitin ligase Von Hippel-Lindau (VHL), which enables effective induction proteasomal degradation...
Abstract One of the characteristics leukemia is that it contains multiple rearrangements signal transduction genes and overexpression non-mutant genes, such as transcription factors. As an important regulator hematopoietic stem cell development erythropoiesis, LMO2 considered effective carcinogenic driver in T lines a marker poor prognosis patients with AML normal karyotype. LDB1 key factor transformation thymocytes into T-ALL induced by LMO2, enhances stability related proteins leukemia....
Glioblastoma multiforme (GBM) is the most common and aggressive brain tumor with a poor prognosis. The growth of GBM cells depends on core transcriptional apparatus, thus rendering RNA polymerase (RNA pol) complex as candidate therapeutic target. pol II subunit B (POLR2B) gene encodes second largest (RPB2); however, its genomic status function in remain unclear. Certain data sets cBioPortal were used for investigating expression POLR2B GBM. RPB2 was analyzed following knockdown by shRNA...
Autophagy has dual roles in cancer, resulting cellular adaptation to promote either cell survival or death. Modulating autophagy can enhance the cytotoxicity of many chemotherapeutic and targeted drugs is increasingly considered be a promising cancer treatment approach. Cynaropicrin (CYN) natural compound that was isolated from an edible plant (artichoke). Previous studies have shown CYN exhibits antitumor effects several lines. However, it anticancer against neuroblastoma (NB) underlying...
Neuroblastoma (NB) is the most common solid tumor of neural crest cell origin in children and has a poor prognosis high-risk patients. The oncogene MYCN was found to be amplified at extremely high levels approximately 20% neuroblastoma cases. In recent years, research on targeted hydrolysis BRD4 indirectly inhibit transcription created by proteolysis targeting chimaera (PROTAC) technology become very popular. dBET57 (S0137, Selleck, TX, USA) novel potent heterobifunctional small molecule...
Abnormal lipid metabolism is one of the most prominent metabolic changes in cancer. Studies have shown that also plays an important role neuroblastoma. We recently discovered insulinoma-associated 2 gene (INSM2) could regulate neuroblastoma (NB) and improperly controlled by super enhancers, a mammalian genome region has been to control expression NB cell identity genes. However, specific molecular pathways which INSM2 leads disease development are unknown. identified as regulated enhancers...
B-cell acute lymphoblastic leukemia (B-ALL) is the most prevalent malignant tumor affecting children. While majority of B-ALL patients (90%) experience successful recovery, early relapse cases continue to exhibit high mortality rates. MZ1, a novel inhibitor Bromodomains and extra-terminal (BET) proteins, has demonstrated potent antitumor activity against hematological malignancies. The objective this study was examine role therapeutic potential MZ1 in treatment B-ALL.In order ascertain...
Osteosarcoma (OS) is one of the most common primary malignant tumors bone in children, which develops from osteoblasts and typically occurs during rapid growth phase bone. Recently, Super-Enhancers(SEs)have been reported to play a crucial role osteosarcoma metastasis. Therefore, there an urgent need identify specific targeted inhibitors SEs assist clinical therapy. This study aimed elucidate BRD4 inhibitor GNE-987 targeting OS preliminarily explore its mechanism. We evaluated changes cells...
Abstract Background: Acute myeloid leukemia (AML) is a common hematological malignancy in children, with poor treatment effect and prognosis. Recent studies have shown that bromodomain terminal protein inhibitors are promising antitumor drugs. As new type of BRD4 PROTAC degradation agent, GNE-987 can slow down the growth rate variety tumors cause apoptosis, which has broad clinical prospects. However, role AML unclear. This study aims to explore therapeutic its underlying mechanism. Methods:...