Wang lan, Shanghai Institute of Nutrition and Health,2023.12.11

Description

Aberrant self-renewal of leukemia initiation cells (LICs) drives aggressive acute myeloid leukemia (AML). Here, we report that UHRF1, an epigenetic regulator that recruits DNMT1 to methylate DNA, is highly expressed in AML and predicts poor prognosis. UHRF1 is required for myeloid leukemogenesis by maintaining self-renewal of LICs. Mechanistically, UHRF1 directly interacts with Sin3A associated protein 30 (SAP30) through two amino acids, G572 and F573 in its SRA domain, to repress gene expression. Depletion of UHRF1 or SAP30 derepresses an important target gene, MXD4, which encodes a MYC antagonist, and leads to suppression of leukemogenesis. Knockdown of MXD4 can rescue the leukemogenesis by activating the MYC pathway. Lastly, we identified a UHRF1 inhibitor, UF146, and demonstrated its significant therapeutic efficacy in the myeloid leukemia PDX model. Taken together, these studies reveal the mechanisms for altered epigenetic programs in AML and provide a promising targeted therapeutic strategy against AML.

OEP004818

Jinxin Xu, Xiamen University,2023.03.12

Description

OEP004010

Lunshan Xu, Army Medical University Daping Hospital: Third Military Medical University Daping Hospital,2024.02.02

Description

Glioblastoma (GBM) is the most aggressive brain tumor type with worse clinical outcome, due to the hallmarks of strong invasiveness, high rate of recurrence and therapeutic resistance to temozolomide (TMZ), the first-line drug for GBM, representing a major challenge for successful GBM therapeutics. Understanding the underlying mechanisms that drive GBM progression will shed novel insight on therapeutic strategies. Receptor-type tyrosine-protein phosphatase S (PTPRS) is a frequently mutated gene in human cancers, including GBM. Its role in GBM has not yet clarified. Here, inactivating PTPRS mutation or deficiency were frequently found in GBM, and deficiency in PTPRS significantly induced defects in G2M checkpoint and limited GBM cells proliferation, leading to potent resistance to TMZ treatment in vitro and in vivo. Surprisingly, loss of PTPRS triggered an unexpected mesenchymal phenotype that markedly enhances migratory capabilities of GBM cells through upregulating numerous matrix metalloproteinases (MMPs) via MAPK-MEK-ERK signaling. Therefore, this work provides a therapeutic window for precisely excluding PTPRS-mutated patients that does not respond to TMZ.

OEP005053

Wang Zeqing, The Interdisciplinary Research Center on Biology and Chemistry,2022.07.07

Description

OEP003508

Yihua Sun, ,2020.03.22

Description

We addressed the microbial composition, community assembly, and nitrogen metabolism in the oxygen minimum zones (OMZs) in Yangtze Estuary water using 16S rRNA gene sequencing, modeling, and metagenomics analyses.

OEP000802

Xinxu Zhang, Shenzhen University,2022.12.08

Description

The sediment sample is collected from the Mariana Trench slope in the western Pacific Ocean at the water depth of 8300 mbsl.

OEP003780

Lei Zhang, Shandong University,2024.01.31

Description

We transplanted gut microbiota from human donors with ASD or typically developing (TD) controls into antibiotic-treated mice. We analysed DNA methylation of specific target genes of both parental and offspring mice.

OEP005039

Hongmei Wang, China university of geosciences,2023.12.01

Description

OEP004782

Jin Zeng, Nanjing Institute of Geography and Limnology, Chinese Academy of Sciences,2021.09.17

Description

samples in wetland of the Tibetan Plateau

OEP002737

shenbing shan, Lingang Laboratory,2024.01.03

Description

Our understanding of the underlying mechanisms for central nervous system metastasis (CNSm), including leptomeningeal metastasis (LM) and brain parenchymal metastasis (BM), is limited. To address this, we conducted single-cell RNA sequencing on 24 patients with CNSm to decipher and compare the tumor microenvironment (TME) of LM and BM. Our results reveal that the TME of LM is more immunosuppressive, characterized by reduced lymphocytes and an increased presence of SPP1+ myeloid cells compared to BM. Additionally, we observed TLS-like structures in a few BM samples, associated with a favorable response to TKI therapy. Furthermore, we explored the correlation between the endothelial cell subtype Endo2 and tumor volume in BM, and systematically compared blood-brain barrier (BBB) cells in CNSm to normal conditions, revealing significant phenotypic remodeling. These findings provide insights into the clinical differences between BM and LM and contribute to a better understanding and clinical treatment of CNSm.

OEP004944