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10. Ubiquitin‐specific protease 22 controls melanoma metastasis and vulnerability to ferroptosis through targeting SIRT1/PTEN/PI3K signaling.

Author

Sun, Huiyan, Meng, Yu, Yao, Lei, Du, Songtao, Li, Yayun, Zhou, Qian, Liu, Yihuang, Dian, Yating, Sun, Yuming, Wang, Xiaomin, Liang, Xiao‐wei, Deng, Guangtong, Chen, Xiang, and Zeng, Furong

Subjects
DEUBIQUITINATING enzymes, MELANOMA, METASTASIS, GENE silencing, EPITHELIAL-mesenchymal transition, DACARBAZINE
Abstract

Metastasis is a major contributing factor that affects the prognosis of melanoma patients. Nevertheless, the underlying molecular mechanisms involved in melanoma metastasis are not yet entirely understood. Here, we identified ubiquitin‐specific protease 22 (USP22) as a pro‐oncogenic protein in melanoma through screening the survival profiles of 52 ubiquitin‐specific proteases (USPs). USP22 demonstrates a strong association with poor clinical outcomes and is significantly overexpressed in melanoma. Ablation of USP22 expression remarkably attenuates melanoma migration, invasion, and epithelial–mesenchymal transition in vitro and suppresses melanoma metastasis in vivo. Mechanistically, USP22 controls melanoma metastasis through the SIRT1/PTEN/PI3K pathway. In addition, we conducted an United States Food and Drug Administration‐approved drug library screening and identified topotecan as a clinically applicable USP22‐targeting molecule by promoting proteasomal degradation of USP22. Finally, we found that both pharmacological and genetic silence of USP22 sensitize RSL3‐induced ferroptosis through suppressing the PI3K/Akt/mTOR pathway and its downstream SCD, and ferroptosis inhibitor could partly rescued the decreased lung metastasis by topotecan in vivo. Overall, our findings reveal a prometastatic role of USP22 and identify topotecan as a potent USP22‐targeting drug to limit melanoma metastasis. [ABSTRACT FROM AUTHOR]

Published
2024
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15. Beclin 2 negatively regulates innate immune signaling and tumor development

Author

Zhu, Motao, Deng, Guangtong, Tan, Peng, Xing, Changsheng, Guan, Cuiping, Jiang, Chongming, Zhang, Yinlong, Ning, Bo, Li, Chaoran, Yin, Bingnan, Chen, Kaifu, Zhao, Yuliang, Wang, Helen Y., Levine, Beth, Nie, Guangjun, and Wang, Rong-Fu

Subjects
Cytokines, Obesity -- Development and progression, Inflammation -- Development and progression, Non-Hodgkin's lymphomas -- Development and progression, B cells, Health care industry
Abstract

Beclin 2 plays a critical role in metabolic regulation and obesity, but its functions in innate immune signaling and cancer development remain largely unknown. Here, we identified Beclin 2 as a critical negative regulator of inflammation and lymphoma development. Mice with homozygous ablation of BCL2-interacting protein 2 (Becn2) developed splenomegaly and lymphadenopathy and markedly increased ERK1/2 and NF-[kappa]B signaling for proinflammatory cytokine production. Beclin 2 targeted the key signaling kinases MEKK3 and TAK1 for degradation through an ATG9A-dependent, but ATG16L/ Beclin 1/LC3-independent, autophagic pathway. Mechanistically, Beclin 2 recruited MEKK3 or TAK1 through ATG9A to form a complex (Beclin 2-ATG9A-MEKK3) on [ATG9A.sup.+] vesicles upon ULK1 activation. Beclin 2 further interacted with STX5 and STX6 to promote the fusion of MEKK3- or TAK1-associated [ATG9A.sup.+] vesicles to phagophores for subsequent degradation. Importantly, Becn2-deficient mice had a markedly increased incidence of lymphoma development, with persistent STAT3 activation. Myeloid-specific ablation of MEKK3 (Map3k3) completely rescued the phenotypes (splenomegaly, higher amounts of proinflammatory cytokines, and cancer incidence) of Becn2-deficient mice. Hence, our findings have identified an important role of Beclin 2 in the negative regulation of innate immune signaling and tumor development through an ATG9Adependent, but ATG16L/Beclin 1/LC3-independent, autophagic pathway, thus providing a potential target for the treatment of inflammatory diseases and cancer., Introduction Autophagy is an essential cellular process for maintaining cell homeostasis and attenuating cell stresses through a 'self-eating' mechanism. Many autophagy-related (ATG) proteins have been identified as functioning in autophagy [...]

Published
2020
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33. Disulfidptosis: a new form of regulated cell death for cancer treatment.

Author

Meng, Yu, Chen, Xiang, and Deng, Guangtong

Subjects
CELL death, CANCER cells, CANCER treatment, CYTOSKELETON, PENTOSE phosphate pathway
Abstract

The supplementation of cystine also induced disulfidptosis in cancer cells with SLC7A11 low expression, accompanied by intracellular NADPH depletion, aberrant disulfide frormation in actin cytoskeleton and F-actin contraction. A recent study published in I Nature Cell Biology i demonstrated a novel type of regulated cell death (RCD) termed disulfidptosis that is caused by excessive disulfide formation in actin cytoskeleton and actin filament (F-actin) collapse, highlighting a promising anticancer strategy to target disulfidptosis [[1]]. Inhibiting NADPH depletion with cystine starvation, increasing NADPH supply with 2-deoxyglucose (2-DG), or treatment with disulfide-reducing agent 2-ME prevented the retarded migration of these actin cytoskeleton-associated proteins and disulfidptosis. [Extracted from the article]

Published
2023
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37. Nomogram For Preoperative Prediction Of Microvascular Invasion Risk In Hepatocellular Carcinoma

Author

Deng, Guangtong, Yao, Lei, Zeng, Furong, Xiao, Liang, and Wang, Zhiming

Subjects
nomogram, independent risk factors, MVI, Cancer Management and Research, microvascular invasion, hepatocellular carcinoma, HCC, preoperative prediction, Original Research
Abstract

Guangtong Deng,1 Lei Yao,1 Furong Zeng,2 Liang Xiao,1,* Zhiming Wang1,* 1General Surgery Department, Xiangya Hospital, Central South University, Changsha, People’s Republic of China; 2Xiangya School of Medicine, Central South University, Changsha, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhiming Wang; Liang XiaoGeneral Surgery Department, Xiangya Hospital, Central South University, Xiangya Road 87, Changsha 410008, People’s Republic of ChinaTel +8618773132682Email a846957007@163.com; xiaoliangrick@csu.edu.cnObjective: To preoperatively predict the microvascular invasion (MVI) risk in hepatocellular carcinoma (HCC) using nomogram.Methods: A retrospective cohort of 513 patients with HCC hospitalized at Xiangya Hospital between January 2014 and December 2018 was included in the study. Univariate and multivariate analysis was performed to identify the independent risk factors for MVI. Based on the independent risk factors, nomogram was established to preoperatively predict the MVI risk in HCC. The accuracy of nomogram was evaluated by using receiver operating characteristic (ROC) curve, calibration curve and decision curve analysis (DCA).Results: Tumor size (OR=1.17, 95% CI: 1.11–1.23, p

Published
2019

38. A predictive model for the severity of COVID-19 in elderly patients

Author

Zeng, Furong, primary, Deng, Guangtong, additional, Cui, Yanhui, additional, Zhang, Yan, additional, Dai, Minhui, additional, Chen, Lingli, additional, Han, Duoduo, additional, Li, Wen, additional, Guo, Kehua, additional, Chen, Xiang, additional, Shen, Minxue, additional, and Pan, Pinhua, additional

Published
2020
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47. CD147 as a Novel Prognostic Biomarker for Hepatocellular Carcinoma: A Meta-Analysis

Author

Peng, Fei, Li, Hui, You, Qian, Li, Hongru, Wu, Dongwen, Jiang, Chunxiang, Deng, Guangtong, Li, Yan, Li, Yuyan, and Wu, Yi

Subjects
Article Subject
Abstract

We conducted a meta-analysis to investigate the controversial association of CD147 expression with HCC prognosis and clinicopathological characteristics. Eight studies from PubMed (1966–2016), EMBASE (1980–2016), Cochrane Library (1996–2016), Web of Science (1945–2016), China National Knowledge Infrastructure (1982–2016), and Wanfang databases (1988–2016) were considered. The associations between CD147 expression and clinicopathological parameters and overall survival (OS) or DFS/RFS were reassessed using the meta-analysis for odds ratio (OR) or hazard ratio (HR) and 95% confidence interval (CI). CD147 expression was associated with DFS/RFS (HR = 3.26; 95% CI: 1.82–5.83; P

Published
2017
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