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| 1 | Serum semaphorin 4C as a diagnostic biomarker in breast cancer:A multicenter retrospective study显示文摘Background:To date,there is no approved blood-based biomarker for breast cancer detection.Herein,we aimed to assess semaphorin 4C(SEMA4C),a pivotal protein involved in breast cancer progression,as a serum diagnostic biomarker.Methods:We included 6,213 consecutive inpatients from Tongji Hospital,Qilu Hospital,and Hubei Cancer Hospital.Training cohort and two validation cohorts were introduced for diagnostic exploration and validation.A pan-cancer cohort was used to independently explore the diagnostic potential of SEMA4C among solid tumors.Breast cancer patients who underwent mass excision prior to modified radical mastectomy were also analyzed.We hypothesized that increased pretreatment serum SEMA4C levels,measured using optimized in-house enzymelinked immunosorbent assay kits,could detect breast cancer.The endpoints were diagnostic performance,including area under the receiver operating characteristic curve(AUC),sensitivity,and specificity.Post-surgery pathological diagnosis was the reference standard and breast cancer staging followed the TNM classification.There was no restriction on disease stage for eligibilities.Results:We included 2667 inpatients with breast lesions,2378 patients with other solid tumors,and 1168 healthy participants.Specifically,118 patients with breast cancer were diagnosed with stage 0(5.71%),620 with stage I(30.00%),966 with stage II(46.73%),217 with stage III(10.50%),and 8 with stage IV(0.39%).Patients with breast cancer had significantly higher serum SEMA4C levels than benign breast tumor patients and normal controls(P<0.001).Elevated serum SEMA4C levels had AUC of 0.920(95%confidence interval[CI]:0.900–0.941)and 0.932(95%CI:0.911–0.953)for breast cancer detection in the two validation cohorts.The AUCs for detecting early-stage breast cancer(n=366)and ductal carcinoma in situ(n=85)were 0.931(95%CI:0.916–0.946)and 0.879(95%CI:0.832–0.925),respectively.Serum SEMA4C levels significantly decreased after surgery,and the reduction was more striking after modified radical mastectomy,compared with mass excision(P<0.001).The positive rate of enhanced serum SEMA4C levels was 84.77%for breast cancer and below 20.75%for the other 14 solid tumors.Conclusions:Serum SEMA4C demonstrated promising potential as a candidate biomarker for breast cancer diagnosis.However,validation in prospective settings and by other study groups is warranted. | Ya Wang Long Qiao Jie Yang Xiong Li Yaqi Duan Jiahao Liu Shaoqi Chen Huayi Li Dan Liu Tian Fang Jingjing Ma Xiaoting Li Fei Ye Junxiang Wan Juncheng Wei Qin Xu Ensong Guo Ping Jin Mingfu Wu Lin Zhang Yun Xia Yaqun Wu Jun Shao Yaojun Feng Qing Zhang Zongyuan Yang Gang Chen Qinghua Zhang Xingrui Li Shixuan Wang Junbo Hu Xiaoyun Wang Mona P.Tan Kazuaki Takabe Beihua Kong Qifeng Yang Ding Ma Qinglei Gao | 2021 | Cancer Communications2021，41，12： | 3 |
| 2 | HIF-1α promotes SARS-CoV-2 infection and aggravates inflammatory responses to COVID-19显示文摘Cytokine storm induced by Severe Acute Respiratory Syndrome Coronavirus 2(SARS-CoV-2)is a major pathological feature of Coronavirus Disease 2019(COVID-19)and a crucial determinant in COVID-19 prognosis.Understanding the mechanism underlying the SARS-CoV-2-induced cytokine storm is critical for COVID-19 control.Here,we identify that SARS-CoV-2 ORF3a and host hypoxia-inducible factor-1α(HIF-1α)play key roles in the virus infection and pro-inflammatory responses. | Mingfu Tian Weiyong Liu Xiang Li Peiyi Zhao Muhammad Adnan Shereen Chengliang Zhu Shanyu Huang Siyu Liu Xiao Yu Miaomiao Yue Pan Pan Wenbiao Wang Yongkui Li Xulin Chen Kailang Wu Zhen Luo Qiwei Zhang Jianguo Wu | 2021 | Signal Transduction and Targeted Therapy2021，6，9： | 1 |
| 3 | Hypoxia signaling in human health and diseases:implications and prospects for therapeutics显示文摘Molecular oxygen(O2)is essential for most biological reactions in mammalian cells.When the intracellular oxygen content decreases,it is called hypoxia.The process of hypoxia is linked to several biological processes,including pathogenic microbe infection,metabolic adaptation,cancer,acute and chronic diseases,and other stress responses.The mechanism underlying cells respond to oxygen changes to mediate subsequent signal response is the central question during hypoxia.Hypoxia-inducible factors(HIFs)sense hypoxia to regulate the expressions of a series of downstream genes expression,which participate in multiple processes including cell metabolism,cell growth/death,cell proliferation,glycolysis,immune response,microbe infection,tumorigenesis,and metastasis.Importantly,hypoxia signaling also interacts with other cellular pathways,such as phosphoinositide 3-kinase(PI3K)-mammalian target of rapamycin(mTOR)signaling,nuclear factor kappa-B(NF-κB)pathway,extracellular signal-regulated kinases(ERK)signaling,and endoplasmic reticulum(ER)stress.This paper systematically reviews the mechanisms of hypoxia signaling activation,the control of HIF signaling,and the function of HIF signaling in human health and diseases.In addition,the therapeutic targets involved in HIF signaling to balance health and diseases are summarized and highlighted,which would provide novel strategies for the design and development of therapeutic drugs. | Zhen Luo Mingfu Tian Ge Yang Qiaoru Tan Yubing Chen Geng Li Qiwei Zhang Yongkui Li Pin Wan Jianguo Wu | 2022 | Signal Transduction and Targeted Therapy2022，7，8： | 1 |
| 4 | SARS-CoV-2 N protein enhances the anti-apoptotic activity of MCL-1 to promote viral replication显示文摘Viral infection in respiratory tract usually leads to cell death,impairing respiratory function to cause severe disease.However,the diversity of clinical manifestations of SARS-CoV-2 infection increases the complexity and difficulty of viral infection prevention,and especially the high-frequency asymptomatic infection increases the risk of virus transmission.Studying how SARS-CoV-2 affects apoptotic pathway may help to understand the pathological process of its infection.Here,we uncovered SARS-CoV-2 imployed a distinct anti-apoptotic mechanism via its N protein.We found SARS-CoV-2 virus-like particles(trVLP)suppressed cell apoptosis,but the trVLP lacking N protein didn’t.Further study verified that N protein repressed cell apoptosis in cultured cells,human lung organoids and mice.Mechanistically,N protein specifically interacted with anti-apoptotic protein MCL-1,and recruited a deubiquitinating enzyme USP15 to remove the K63-linked ubiquitination of MCL-1,which stabilized this protein and promoted it to hijack Bak in mitochondria.Importantly,N protein promoted the replications of IAV,DENV and ZIKV,and exacerbated death of IAV-infected mice,all of which could be blocked by a MCL-1 specific inhibitor,S63845.Altogether,we identifed a distinct anti-apoptotic function of the N protein,through which it promoted viral replication.These may explain how SARS-CoV-2 effectively replicates in asymptomatic individuals without cuasing respiratory dysfunction,and indicate a risk of enhanced coinfection with other viruses.We anticipate that abrogating the N/MCL-1-dominated apoptosis repression is conducive to the treatments of SARS-CoV-2 infection as well as coinfections with other viruses. | Pan Pan Weiwei Ge Zhiwei Lei Wei luo Yuqing Liu Zhanwen Guan Lumiao Chen Zhenyang Yu Miaomiao Shen Dingwen Hu Qi Xiang Wenbiao Wang Pin Wan Mingfu Tian Yang Yu Zhen Luo Xulin Chen Heng Xiao Qiwei Zhang Xujing Liang Xin Chen Yongkui Li Jianguo Wu | 2023 | Signal Transduction and Targeted Therapy2023，8，6： | 0 |
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