Yan Shen

Nanjing University

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Qiang Xu

Nanjing University

Yang Sun

Nanjing University

Xuefeng Wu

Zhejiang Industry Polytechnic College

Xudong Wu

Ningxia Academy of Agriculture and Forestry Sciences

Jian Gao

Nanjing University

Wenjie Guo

Nanjing University

Yanhong Gu

Jiangsu Province Hospital

Xuefeng Wu

Nanjing Drum Tower Hospital

Wenwen Xue

Shanghai Eye Disease Prevention & Treatment Center

Hui Ming Ge

Hebei University of Technology

Cooperative Institutions

Nanjing University

155

Chinese Academy of Medical Sciences & Peking Union Medical College

149

Chinese Academy of Sciences

126

Huazhong University of Science and Technology

Shanghai Jiao Tong University

Nanjing Medical University

Peking University

Sun Yat-sen University

Wuhan University

Capital Medical University

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Proteomics screen to reveal molecular changes mediated by C722G missense mutation in CHRM2 gene

Journal of Proteomics (2013)

Dongyan Hou Ying Chen Jiamei Liu Lin Xu Zhiyong Zhang

10.1016/j.jprot.2013.05.027

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Citations (6)

Diptoindonesin G promotes ERK-mediated nuclear translocation of p-STAT1 (Ser727) and cell differentiation in AML cells

Cell Death and Disease (2017)

Jian Gao Minmin Fan Gang Xiang Jujuan Wang Xiong Zhang

Abstract Exploration of a new differentiation therapy that extends the range of differentiation for treating acute myeloid leukemia (AML) is attractive to researchers and clinicians. Here we report that diptoindonesin G (Dip G), a natural resveratrol aneuploid, exerts antiproliferative activity by inducing G2/M phase arrest and cell differentiation in AML cell lines and primary AML cells. Gene-profiling experiments showed that treating human leukemia HL-60 cells with Dip G was associated with a remarkable upregulation of STAT1 target gene expression, including IFIT3 and CXCL10. Mechanistically, Dip G activated ERK, which caused phosphorylation of STAT1 at Ser727 and selectively enhanced the interaction of p-STAT1 (Ser727) and p-ERK, further promoting their nuclear translocation. The nuclear translocation of p-STAT1 and p-ERK enhanced the transactivation of STAT1-targeted genes in AML cells. Furthermore, in vivo treatment of HL-60 xenografts demonstrated that Dip G significantly inhibited tumor growth and reduced tumor weight by inducing cell differentiation. Taken together, these results shed light on an essential role for ERK-mediated nuclear translocation of p-STAT1 (Ser727) and its full transcriptional activity in Dip G-induced differentiation of AML cells. Furthermore, these results demonstrate that Dip G could be used as a differentiation-inducing agent for AML therapy, particularly for non-acute promyelocytic leukemia therapy.

STAT1

10.1038/cddis.2017.159

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Citations (30)

Preferential cytotoxicity of bortezomib toward highly malignant human liposarcoma cells via suppression of MDR1 expression and function

Toxicology and Applied Pharmacology (2015)

Yamei Hu Lingxian Wang Lu Wang Xuefeng Wu Xudong Wu

10.1016/j.taap.2014.12.015

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Citations (6)

(+)-Borneol improves the efficacy of edaravone against DSS-induced colitis by promoting M2 macrophages polarization via JAK2-STAT3 signaling pathway

International Immunopharmacology (2017)

Xiong Zhang Fang Xu Li Liu Lili Feng Xuefeng Wu

Edaravone

10.1016/j.intimp.2017.10.002

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Citations (43)

Selective Sequestration of STAT1 in the Cytoplasm via Phosphorylated SHP-2 Ameliorates Murine Experimental Colitis

The Journal of Immunology (2012)

Xingxin Wu Wenjie Guo Limei Wu Yanhong Gu Liyun Gu

The side effects of current immunosuppressive drugs have impeded the development of therapies for immune diseases. Selective regulation of STAT signaling is an attractive strategy for treating immune disorders. In this study, we used a small-molecule compound to explore possible means of targeting STAT1 for the treatment of Th1-mediated inflammation. Selective regulation of STAT1 signaling in T cells from C57BL/6 mice was accomplished using fusaruside, a small-molecule compound that triggers the tyrosine phosphorylation of Src homology 2-containing protein tyrosine phosphatase 2 (SHP-2). The interaction of tyrosine phosphorylated SHP-2 (pY-SHP-2) with cytosolic STAT1 prevented the recruitment of STAT1 to IFN-γR and specifically inhibited STAT1 signaling, resulting in a reduction in Th1 cytokine production and an improvement in 2, 4, 6-trinitrobenzene sulfonic acid-induced colitis in mice. Blocking the pY-SHP-2-STAT1 interaction, with SHP-2 inhibitor NSC-87877 or using T cells from conditional SHP-2 knockout mice, reversed the effects of fusaruside, resulting in STAT1 activation and worsened colitis. The fusaruside-induced ability of pY-SHP-2 to selectively sequestrate STAT1 from recruitment to the receptor is independent of its function as a phosphatase, demonstrating a novel role for SHP-2 in regulating both STAT1 signaling and Th1-type immune responses. These findings could lead to increased options for the treatment of Crohn's disease and other Th1-mediated inflammatory diseases.

STAT1

Cell Signaling

10.4049/jimmunol.1201006

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Citations (51)

Induced pluripotent stem cells and Parkinson's disease: modelling and treatment

Cell Proliferation (2016)

Xiaoyun Xu Jinsha Huang Jie Li Ling Liu Chao Han

Abstract Many neurodegenerative disorders, such as Parkinson's disease ( PD ), are characterized by progressive neuronal loss in different regions of the central nervous system, contributing to brain dysfunction in the relevant patients. Stem cell therapy holds great promise for PD patients, including with foetal ventral mesencephalic cells, human embryonic stem cells ( hESC s) and human induced pluripotent stem cells (hi PSC s). Moreover, stem cells can be used to model neurodegenerative diseases in order to screen potential medication and explore their mechanisms of disease. However, related ethical issues, immunological rejection and lack of canonical grafting protocols limit common clinical use of stem cells. iPSC s, derived from reprogrammed somatic cells, provide new hope for cell replacement therapy. In this review, recent development in stem cell treatment for PD , using hi PSC s, as well as the potential value of hi PSC s in modelling for PD , have been summarized for application of iPSC s technology to clinical translation for PD treatment.

Cell therapy

Stem Cell Therapy

10.1111/cpr.12229

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Citations (16)

Small-molecule RL71-triggered excessive autophagic cell death as a potential therapeutic strategy in triple-negative breast cancer

Cell Death and Disease (2017)

Jian Gao Minmin Fan Shuang Peng Minxia Zhang Gang Xiang

Triple-negative breast cancer (TNBC) has an aggressive phenotype and a poor prognosis owing to the high propensity for metastatic progression and the absence of specific targeted treatment. Here, we revealed that small-molecule RL71 targeting sarco/endoplasmic reticulum calcium-ATPase 2 (SERCA2) exhibited potent anti-cancer activity on all TNBC cells tested. Apart from apoptosis induction, RL71 triggered excessive autophagic cell death, the main contributor to RL71-induced TNBC cell death. RL71 augmented the release of Ca2+ from the endoplasmic reticulum (ER) into the cytosol by inhibiting SERCA2 activity. The disruption of calcium homeostasis induced ER stress, leading to apoptosis. More importantly, the elevated intracellular calcium signals induced autophagy through the activation of the CaMKK-AMPK-mTOR pathway and mitochondrial damage. In two TNBC xenograft mouse models, RL71 also displayed strong efficacy including the inhibition of tumor growth, the reduction of metastasis, as well as the prolongation of survival time. These findings suggest SERCA2 as a previous unknown target candidate for TNBC treatment and support the idea that autophagy inducers could be useful as new therapeutics in TNBC treatment.

Triple-negative breast cancer

10.1038/cddis.2017.444

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Prognostic Role of Circulating Exosomal miR-425-3p for the Response of NSCLC to Platinum-Based Chemotherapy

Cancer Epidemiology Biomarkers & Prevention (2018)

Daolu Yuwen Yuzhu Ma Deqiang Wang Jian Gao Xin Li

Platinum-based doublets with a third-generation agent are the recommended option for many patients with non-small cell lung cancer (NSCLC) with no contraindications to platinum compounds. Unfortunately, the clinical effectiveness of such chemotherapy is limited by intrinsic or acquired resistance.Circulating exosomal miRNAs were isolated and used to perform HiSeq deep-sequencing analyses on serum pool samples from platinum-resistant or platinum-sensitive patients, and six exosomal miRNAs were further validated for their predictive utility by qRT-PCR in 170 serum samples of patients with advanced NSCLC. Gain- and loss-of-function experiments clarified the responsiveness regulating role of the clinically relevant miRNA. IHC analyses were performed to evaluate the association between basal autophagy in lung cancer tissues and responsiveness in 203 patients with NSCLC receiving platinum-based chemotherapy.Six circulating exosomal miRNAs (miR-425-3p, miR-1273h, miR-4755-5p, miR-9-5p, miR-146a-5p, and miR-215-5p) were found to be differentially expressed with the largest fold change in platinum-resistant patients compared with platinum-sensitive patients. High miR-425-3p proved to be a potent predictive biomarker for low responsiveness and poor progression-free survival (PFS). Mechanistically, miR-425-3p upregulated the autophagic levels via targeting AKT1, leading to the decrease in therapeutic response. Concordantly, high levels of basal autophagy in lung cancer tissues correlate with low responsiveness in patients with NSCLC within the early and advanced disease stages.Our study highlights circulating exosomal miR-425-3p as a potential biomarker for improved predictions of the clinical response to platinum-based chemotherapy in patients with NSCLC.This study provides the first evidence that miR-425-3p in NSCLC patient-derived exosomes can be a marker for predicating the clinical response to platinum-based chemotherapy.

10.1158/1055-9965.epi-18-0569

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Citations (88)

Suppression of NF-κB signaling and NLRP3 inflammasome activation in macrophages is responsible for the amelioration of experimental murine colitis by the natural compound fraxinellone

Toxicology and Applied Pharmacology (2014)

Xuefeng Wu Zijun Ouyang Lili Feng Gong Chen Wenjie Guo

10.1016/j.taap.2014.10.002

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Citations (85)

Small molecule-mediated upregulation of CCR7 ameliorates murine experimental autoimmune encephalomyelitis by accelerating T-cell homing

International Immunopharmacology (2017)

Xin Li Tingting Lu Wenwen Xue Yixuan Wang Qiong Luo