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| 1 | miR-7/TGF-β2 axis sustains acidic tumor microenvironment-induced lung cancer metastasis显示文摘Acidosis,regardless of hypoxia involvement,is recognized as a chronic and harsh tumor microenvironment(TME)that educates malignant cells to thrive and metastasize.Although overwhelming evidence supports an acidic environment as a driver or ubiquitous hallmark of cancer progression,the unrevealed core mechanisms underlying the direct effect of acidification on tumorigenesis have hindered the discovery of novel therapeutic targets and clinical therapy.Here,chemical-induced and transgenic mouse models for colon,liver and lung cancer were established,respectively.miR-7 and TGF-β2 expressions were examined in clinical tissues(n=184).RNA-seq,miRNA-seq,proteomics,biosynthesis analyses and functional studies were performed to validate the mechanisms involved in the acidic TME-induced lung cancer metastasis.Our data show that lung cancer is sensitive to the increased acidification of TME,and acidic TME-induced lung cancer metastasis via inhibition of miR-7-5 p.TGF-β2 is a direct target of miR-7-5 p.The reduced expression of miR-7-5 p subsequently increases the expression of TGF-β2 which enhances the metastatic potential of the lung cancer.Indeed,overexpression of miR-7-5 p reduces the acidic p H-enhanced lung cancer metastasis.Furthermore,the human lung tumor samples also show a reduced miR-7-5 p expression but an elevated level of activated TGF-β2;the expressions of both miR-7-5 p and TGF-β2 are correlated with patients’survival.We are the first to identify the role of the miR-7/TGF-β2 axis in acidic p H-enhanced lung cancer metastasis.Our study not only delineates how acidification directly affects tumorigenesis,but also suggests miR-7 is a novel reliable biomarker for acidic TME and a novel therapeutic target for non-small cell lung cancer(NSCLC)treatment.Our study opens an avenue to explore the p H-sensitive subcellular components as novel therapeutic targets for cancer treatment. | Tao Su Suchao Huang Yanmin Zhang Yajuan Guo Shuwei Zhang Jiaji Guan Mingjing Meng Linxin Liu Caiyan Wang Dihua Yu Hiu-Yee Kwan Zhiying Huang Qiuju Huang Elaine Lai-Han Leung Ming Hu Ying Wang Zhongqiu Liu Linlin Lu | 2022 | Acta Pharmaceutica Sinica B2022，12，2： | 2 |
| 2 | Effect of tumor necrosis factor inhibitors on rheumatoid arthritis-induced peripheral neuropathy A cohort study显示文摘In this historical cohort study,236 patients with primary rheumatoid arthritis were treated with the tumor necrosis factor inhibitors,etanercept or infliximab(n = 80),or by conventional methods(n = 156).Results revealed that 11 patients developed varying types of peripheral neuropathy at 1-2 years post-treatment(mean 16 months).The incidence of peripheral neuropathy in the tumor necrosis factor inhibitors treatment group was 8.8%(7/80),which was significantly higher than the conventional treatment group(2.6%;4/156).The relative risk of developing peripheral neuropathy in the tumor necrosis factor inhibitors treatment group was 3.41(95% confidence interval:1.03-11.31).Comparison of the tumor necrosis factor inhibitors revealed that etanercept and infliximab had no significant difference in terms of inducing peripheral neuropathy.Experimental findings indicate that tumor necrosis factor inhibitors may increase the risk of peripheral neuropathy. | Naizhi Wang Yingying Guo Lili Yang Wenyi Fu Yanbing Xu Linxin Hou Shuai Zhao Ning Zhang | 2012 | Neural Regeneration Research2012，7，11： | 2 |
| 3 | Modified surgery for acute thoracolumbar fractures=a prospective report显示文摘 | Dasheng Lin Linxin Guo Zhengqi Ding | 2011 | Eur Orthop Traumatol2011，2，： | 1 |
| 4 | Modified surgery for acute thoracolumbar fractures:a prospective report显示文摘 | Dasheng Lin Linxin Guo Zhengqi Ding | 2011 | Eur Orthop Traumatol2011，2，12： | 1 |
| 5 | A YAP/TAZ-CD54 axis is required for CXCR2-CD44-tumor-specific neutrophils to suppress gastric cancer显示文摘As an important part of tumor microenvironment,neutrophils are poorly understood due to their spatiotemporal heterogeneity in tumorigenesis.Here we defined,at single-cell resolution,CD44-CxCR2-neutrophils as tumor-specific neutrophils(tsNeus)in both mouse and human gastric cancer(GC).We uncovered a Hippo regulon in neutrophils with unique YAP signature genes(e.g.,ICAM1,CD14,EGR1)distinct from those identified in epithelial and/or cancer cells.Importantly,knockout of YAP/TAz in neutrophils impaired their differentiation into CD54+tsNeus and reduced their antitumor activity,leading to accelerated GC progression.Moreover,the relative amounts of CD54+tsNeus were found to be negatively associated with GC progression and positively associated with patient survival.Interestingly,GC patients receiving neoadjuvant chemotherapy had increased numbers of CD54+tsNeus.Furthermore,pharmacologically enhancing YAP activity selectively activated neutrophils to suppress refractory GC,with no significant inflammation-related side effects.Thus,our work characterized tumor-specific neutrophils in GC and revealed an essential role of YAP/TAZ-CD54 axis in tsNeus,opening a new possibility to develop neutrophil-based antitumor therapeutics. | Pingping Nie Weihong Zhang Yan Meng Moubin Lin Fenghua Guo Hui Zhang Zhenzhu Tong Meng Wang Fan Chen Liwei An Yang Tang Yi Han Ruixian Yu Wenjia Wang Yuanzhi Xu Linxin Wei Zhaocai Zhou Shi Jiao | 2023 | Protein & Cell2023，14，7： | 0 |
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