期刊：
Frontiers in Genetics,2021年11:571403 ISSN：1664-8021
通讯作者：
Yang, Jing;Liu, Zhifeng
作者机构：
[Hu, Guangsheng; Yang, Jing] Univ South China, Affiliated Hosp 1, Dept Gastroenterol, Hengyang, Peoples R China.;[Peng, Hong; Liu, Zhifeng; Yu, Jing; Jiang, Qingshan; Tang, Yanhua; Li, Shuyan; Liu, Lijun; Wang, Yaya] Univ South China, Affiliated Hosp 1, Dept Otorhinolaryngol, Hengyang, Peoples R China.;[Yang, Jing] Univ South China, Hunan Prov Key Lab Tumor Cellular & Mol Pathol, Canc Res Inst, Hengyang, Peoples R China.
通讯机构：
[Yang, Jing; Liu, Zhifeng] U;Univ South China, Affiliated Hosp 1, Dept Gastroenterol, Hengyang, Peoples R China.;Univ South China, Affiliated Hosp 1, Dept Otorhinolaryngol, Hengyang, Peoples R China.;Univ South China, Hunan Prov Key Lab Tumor Cellular & Mol Pathol, Canc Res Inst, Hengyang, Peoples R China.
关键词：
Squamous cell carcinoma of head and neck (SCCHN);RNA binding proteins (RBPs);Differentially Expressed Genes (DEGs);prognosis;tumor immunity
摘要：
RNA-binding proteins (RBPs) interacting with target RNAs play essential roles in RNA metabolism at the post-transcription level. Perturbations of RBPs can accelerate cancer development and cause dysregulation of the immune cell function and activity leading to evade immune destruction of cancer cells. However, few studies have systematically analyzed the potential prognostic value and functions of RBPs in squamous cell carcinoma of head and neck (SCCHN). Here, for the first time, we comprehensively identified 92 differentially expressed RBPs from The Cancer Genome Atlas (TCGA) database. In the training set, a prognosis risk model was constructed with six RBPs, including NCBP2, MKRN3, MRPL47, AZGP1, IGF2BP2, and EZH2, and validated by the TCGA test set, the TCGA all set, and the GEO data set. In addition, the risk score was related to the clinical stage, T classification, and N classification. Furthermore, the high-risk score was significantly correlated with immunosuppression, and low expression of EZH2 and AZGP1 and high expression of IGF2BP2 were the main factors. Thus, the risk model may serve as a prognostic signature and offer highlights for individualized immunotherapy in SCCHN patients.
摘要：
Atherosclerosis (AS) is characterized by lipids metabolism disorder and inflammatory response. Accumulating evidence has demonstrated that Wingless type 5a (Wnt5a) is implicated in cardiovascular diseases through non-canonical Wnt cascades. However, its precise role during the pathogenesis of AS is still unclear. Therefore, the present study aims to investigate the role and the underlying mechanism of Wnt5a/receptor tyrosine kinase-like orphan receptor 2 (Ror2) pathways in the promotion of AS process through affecting lipid accumulation and inflammation. In atherosclerotic clinical samples, Wnt5a levels were measured by using enzyme-linked immunosorbent assay (ELISA) assay. In vivo experiments were conducted by using apolipoprotein E knockout (apoE(-)(/)(-)) mice model. Vascular smooth muscle cells (VSMCs) were applied for in vitro studies. Wnt5a was highly expressed in both of atherosclerotic clinical samples and apoE(-)(/)(-) mice. The knockdown of Wnt5a significantly inhibited cholesterol accumulation and inflammatory response. Additionally, the lipopolysaccharide (LPS)-induced inflammation aggravated the cholesterol accumulation and decreased adenosine triphosphate (ATP)-binding cassette transporter A1 (ABCA1) expression in VSMCs. Depletion of intracellular cholesterol by beta-cyclodextrin (beta-CD) led to the upregulation of ABCA1 and the inhibition of inflammation. Conversely, the overexpression of Wnt5a inhibited ABCA1 expression, facilitated cholesterol accumulation, impared cholesterol efflux, promoted NF-kappaB nuclear translocation and the inflammatory cytokines secretion. Moreover, the knockdown of Ror2 increased ABCA1 expression and reduced Wnt5a-induced cholesterol accumulation and inflammatory responses. Furthermore, the knockdown of ABCA1 enhanced cholesterol accumulation and inflammatory response. Therefore, Wnt5a/Ror2 pathway was critical in regulating cholesterol homeostasis and inflammatory response, which might be a promising therapeutic target for AS therapy.
期刊：
BLOOD CELLS MOLECULES AND DISEASES,2020年85:102477 ISSN：1079-9796
通讯作者：
Nie, Ling;Zhang, Ji
作者机构：
[Kuang, Yijin; Xiong, Dehui; Liu, Jing; Roy, Mridul; Han, Xu; Peng, Yuanliang; Liang, Long] Cent South Univ, Sch Life Sci, Mol Biol Res Ctr, Changsha 410078, Peoples R China.;[Kuang, Yijin; Xiong, Dehui; Liu, Jing; Roy, Mridul; Han, Xu; Peng, Yuanliang; Liang, Long] Cent South Univ, Sch Life Sci, Ctr Med Genet, Changsha 410078, Peoples R China.;[Kuang, Yijin] Southern Med Univ, Sch Lab Med & Biotechnol, Guangzhou 510515, Peoples R China.;[Nie, Ling; Cao, Pengfei] Cent South Univ, Xiangya Hosp, Hunan Prov Key Lab Basic & Appl Hematol, Dept Hematol, Changsha 410008, Peoples R China.;[Liu, Zhaoping; Xu, Zhenru; Zhang, Ji] South China Univ, Affiliated Hosp 1, Dept Clin Lab, Hengyang 421000, Peoples R China.
通讯机构：
[Nie, Ling] C;[Zhang, Ji] S;Cent South Univ, Xiangya Hosp, Hunan Prov Key Lab Basic & Appl Hematol, Dept Hematol, Changsha 410008, Peoples R China.;South China Univ, Affiliated Hosp 1, Dept Clin Lab, Hengyang 421000, Peoples R China.
关键词：
BCR-ABL;CML;Imatinib;p19INK4d;Proliferation
摘要：
Chronic myeloid leukemia (CML) is a kind of myeloproliferative disorder caused by a constitutively active BCR-ABL tyrosine kinase. Tyrosine kinase inhibitors (TKIs), imatinib and its derivatives, have achieved great progress in the treatment of CML. However, many CML patients do not respond to TKIs alone. p19(INK4d), a cyclin-dependent kinase inhibitor, plays important roles in proliferation, DNA damage repair, apoptosis and cell differentiation, but its role in CML is unknown. Herein, we found that the expression of p19(INK4d) in CML patients was significantly lower than that in healthy controls. p19(INK4d) overexpression inhibits cell proliferation through cell cycle arrest, and cooperates with imatinib to inhibit CML more effectively in vitro and in vivo. Mechanistically, p19(INK4d) decreased the expression of BCR-ABL and its downstream molecules p-Mek1/2, moreover, the expression of Gli-1, c-myc, MUC1, Shh and TC48 also reduced significantly. Collectively, p19(INK4d) inhibits proliferation and enhances imatinib efficacy in the treatment of CML. These findings maybe have implications for developing potential targets to increase imatinib sensitivity for CML.
期刊：
Cancer Letters,2020年495:191-199 ISSN：0304-3835
通讯作者：
Gan, Runliang
作者机构：
[Hu, Guangsheng; Yang, Jing; Zeng, Bin] Univ South China, Dept Gastroenterol, Affiliated Hosp 1, Hengyang 421001, Hunan, Peoples R China.;[Gan, Runliang; Yang, Jing] Univ South China, Canc Res Inst, Hunan Prov Key Lab Tumor Cellular & Mol Pathol, Hengyang 421001, Hunan, Peoples R China.;[Liu, Zhifeng] Univ South China, Dept Otorhinolaryngol, Affiliated Hosp 1, Hengyang 421001, Hunan, Peoples R China.
通讯机构：
[Gan, Runliang] U;Univ South China, Canc Res Inst, Hunan Prov Key Lab Tumor Cellular & Mol Pathol, Hengyang 421001, Hunan, Peoples R China.
关键词：
Gastric cancer;Epstein-barr virus (EBV);Molecular features;Clinicopathological features
摘要：
Epstein-Barr virus (EBV)-associated gastric cancer (EBVaGC) is a common malignant tumor associated with EBV infection. The molecular classification of gastric carcinoma indicates that EBVaGC is a distinct subtype in terms of oncogenesis and molecular features. Viral proteins, Bam-HI-A rightward transcripts (BART) miRNAs, and Bam-HI A rightward frame 1 (BARF1) promote oncogenesis after EBV infection via the induction of methylation, regulation of host gene expression, and malignant transformation. Together with abnormal mutations and amplification of the host genome as driving factors, interactions between the EBV genome and host genome accelerate carcinogenesis. The molecular profile of EBVaGC is that of EBV driving DNA hypermethylation, frequent phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA) mutations, and the overexpression of Janus kinase 2 (JAK2), programmed death ligand-1 (PD-L1), and PD-L2. Clinically, the frequency of lymph node metastasis is lower, and the prognosis is better for EBVaGC than EBV-negative gastric cancer (EBVnGC). Pathologically, EBVaGC is a gastric adenocarcinoma with lymphoid stroma. This review interprets how the EBV genome is involved in the oncogenesis of gastric cancer and describes the molecular and clinicopathological features of EBVaGC.
期刊：
Journal of Hematology & Oncology,2020年13(1):1-19 ISSN：1756-8722
通讯作者：
Liu, Jing;Zhang, Ji
作者机构：
[Yuan, Shunling; Liu, Zhaoping; Xu, Zhenru; Zhang, Ji] Univ South China, Affiliated Hosp 1, Dept Clin Lab, Hengyang 421001, Hunan, Peoples R China.;[Liu, Jing] Cent South Univ, Sch Life Sci, Mol Biol Res Ctr, Hunan Prov Key Lab Basic & Appl Hematol, Changsha 410078, Hunan, Peoples R China.;[Liu, Jing] Cent South Univ, Sch Life Sci, Ctr Med Genet, Changsha 410078, Hunan, Peoples R China.
通讯机构：
[Liu, Jing] C;[Zhang, Ji] U;Cent South Univ, Sch Life Sci, Mol Biol Res Ctr, Hunan Prov Key Lab Basic & Appl Hematol, Changsha 410078, Hunan, Peoples R China.;Cent South Univ, Sch Life Sci, Ctr Med Genet, Changsha 410078, Hunan, Peoples R China.;Univ South China, Affiliated Hosp 1, Dept Clin Lab, Hengyang 421001, Hunan, Peoples R China.
关键词：
High mobility group box 1 (HMGB1);Hematopoietic stem cells (HSCs);Bone marrow (BM) microenvironment;Inflammation;Chemoresistance
摘要：
High mobility group box 1 (HMGB1) is a nonhistone chromatin-associated protein that has been widely reported to play a pivotal role in the pathogenesis of hematopoietic malignancies. As a representative damage-associated molecular pattern (DAMP), HMGB1 normally exists inside cells but can be secreted into the extracellular environment through passive or active release. Extracellular HMGB1 binds with several different receptors and interactors to mediate the proliferation, differentiation, mobilization, and senescence of hematopoietic stem cells (HSCs). HMGB1 is also involved in the formation of the inflammatory bone marrow (BM) microenvironment by activating proinflammatory signaling pathways. Moreover, HMGB1-dependent autophagy induces chemotherapy resistance in leukemia and multiple myeloma. In this review, we systematically summarize the emerging roles of HMGB1 in carcinogenesis, progression, prognosis, and potential clinical applications in different hematopoietic malignancies. In summary, targeting the regulation of HMGB1 activity in HSCs and the BM microenvironment is highly beneficial in the diagnosis and treatment of various hematopoietic malignancies.
通讯机构：
[Qu, Xiaowang] U;Univ South China, Peoples Hosp Chenzhou 1, Translat Med Inst, 102 Luojiajing, Chenzhou 423000, Hunan, Peoples R China.
关键词：
hepatitis B surface antigen;neutralizing antibody;hepatitis B surface antigen;hepatitis C antibody;neutralizing antibody;adult;antibody response;Article;cellular distribution;controlled study;female;flow cytometry;hepatitis B;hepatitis C;human;human cell;major clinical study;male;mixed infection;priority journal;Tfh cell;Th1 cell;Th2 cell;blood;comparative study;cytology;drug use;helper cell;Hepacivirus;hepatitis B;Hepatitis B virus;hepatitis C;immunology;middle aged;T lymphocyte subpopulation;virology;virus load;Adult;Antibodies, Neutralizing;Coinfection;Drug Users;Female;Hepacivirus;Hepatitis B;Hepatitis B Surface Antigens;Hepatitis B virus;Hepatitis C;Hepatitis C Antibodies;Humans;Male;Middle Aged;T-Lymphocyte Subsets;T-Lymphocytes, Helper-Inducer;Viral Load
摘要：
Hepatitis C virus (HCV) and hepatitis B virus (HBV) coinfection reciprocally influences viral replication and host defence responses. This study aimed to investigate the impact of HBV coinfection on circulating T follicular helper cell (cTfh) distribution and the HCV neutralizing antibody (nAb) response. HCV neutralizing antibody responses were measured in individuals with HCV monoinfection (n = 83) and HBV/HCV coinfection (n = 78) using the HCV pseudoparticle neutralization assay. The frequencies of cTfh cells and their subsets in HCV monoinfection (n = 34) and HBV/HCV coinfection (n = 30) were analysed by flow cytometry. The correlations of clinical parameters, cTfh cells and neutralizing antibody responses were analysed. Compared with HCV monoinfection, the HBV coinfection group showed significantly lower HCV neutralizing antibody responses (P < 0.001) and a decreased frequency of circulating Th1-like Tfh cells (Tfh1) (P = 0.004). In HCV monoinfection, the frequency of the Tfh1 subset was positively correlated with HCV neutralizing antibody responses (R = 0.378, P = 0.03), but this correlation was lost under HBV/HCV coinfection (R = 0.115, P = 0.551). In contrast, the frequency of circulating Th2-like Tfh cells (Tfh2) was negatively correlated with the HCV neutralizing antibody responses (R = 0.404, P = 0.003). Further analysis showed that HBV coinfection enhanced the Tfh2 subset composition within cTfh cells (P < 0.001), which was associated with serum HBsAg in HBV/HCV coinfection (R = 0.521, P = 0.003). As expected, HBsAg also exhibited an inverse association with HCV neutralizing antibody responses in HBV/HCV coinfection (R = 0.59, P < 0.001). In contrast to HCV monoinfection, HBV/HCV coinfection leads to altered cTfh cell distribution and impaired HCV neutralizing antibody responses, which are associated with HBsAg. These findings will be helpful for better understanding the immunopathogenesis of HBV/HCV coinfection.
期刊：
American Journal of Human Genetics,2019年105(1):166-176 ISSN：0002-9297
通讯作者：
Shen, Lu;Jin, Peng
作者机构：
[Tian, Yun; Sun, Qi-Ying; Yi, Fang; Tang, Bei-Sha; Zhou, Ya-Fang; Xu, Hong-Wei] Cent S Univ, Xiangya Hosp, Dept Geriatr, Changsha 410008, Hunan, Peoples R China.;[Zeng, Sheng; Jiao, Bin; Liu, Zhen; Chen, Zhao; Jiang, Hong; Zhou, Chao-Jun; Yan, Xin-Xiang; Hou, Xuan; Guo, Ji-Feng; Tang, Bei-Sha; Long, Hong-Yu; Wang, Jun-Ling; Shen, Lu] Cent S Univ, Xiangya Hosp, Dept Neurol, Changsha 410008, Hunan, Peoples R China.;[Tian, Yun; Tang, Bei-Sha; Shen, Lu] Cent S Univ, Xiangya Hosp, Natl Clin Res Ctr Geriatr Disorders, Changsha 410008, Hunan, Peoples R China.;[Xia, Kun; Hu, Zheng-Mao; Huang, Wen; Duan, Ran-Hui] Cent S Univ, Sch Life Sci, Ctr Med Genet, Changsha 410008, Hunan, Peoples R China.;[Kong, Ha Eun; Li, Yujing; Shafik, Andrew Mark; Allen, Emily G.; Jin, Peng] Emory Univ, Sch Med, Dept Human Genet, Whitehead Res Bldg,Room 305A,615 Michael St, Atlanta, GA 30322 USA.
通讯机构：
[Shen, Lu] C;[Jin, Peng] E;Cent S Univ, Xiangya Hosp, Dept Neurol, Changsha 410008, Hunan, Peoples R China.;Cent S Univ, Xiangya Hosp, Natl Clin Res Ctr Geriatr Disorders, Changsha 410008, Hunan, Peoples R China.;Emory Univ, Sch Med, Dept Human Genet, Whitehead Res Bldg,Room 305A,615 Michael St, Atlanta, GA 30322 USA.
摘要：
Neuronal intranuclear inclusion disease (NIID) is a slowly progressing neurodegenerative disease characterized by eosinophilic intranuclear inclusions in the nervous system and multiple visceral organs. The clinical manifestation of NIID varies widely, and both familial and sporadic cases have been reported. Here we have performed genetic linkage analysis and mapped the disease locus to 1p13.3-q23.1; however, whole-exome sequencing revealed no potential disease-causing mutations. We then performed long-read genome sequencing and identified a large GGC repeat expansion within human-specific NOTCH2NLC. Expanded GGC repeats as the cause of NIID was further confirmed in an additional three NIID-affected families as well as five sporadic NIID-affected case subjects. Moreover, given the clinical heterogeneity of NIID, we examined the size of the GGC repeat among 456 families with a variety of neurological conditions with the known pathogenic genes excluded. Surprisingly, GGC repeat expansion was observed in two Alzheimer disease (AD)-affected families and three parkinsonism-affected families, implicating that the GGC repeat expansions in NOTCH2NLC could also contribute to the pathogenesis of both AD and PD. Therefore, we suggest defining a term NIID-related disorders (NIIDRD), which will include NIID and other related neurodegenerative diseases caused by the expanded GGC repeat within human-specific NOTCH2NLC.
通讯机构：
[Qu, Xiaowang] U;[Qu, Xiaowang] S;Univ South China, Peoples Hosp Chenzhou 1, Translat Med Inst, Chenzhou 423000, Hunan, Peoples R China.;Southern Med Univ, Affiliated Peoples Hosp Chenzhou 1, Chenzhou 423000, Hunan, Peoples R China.
摘要：
<jats:title>Abstract</jats:title><jats:p>Circulating T follicular helper (cTfh) cells have been identified as counterparts of germinal center Tfh (GC Tfh) cells in humans and can support T-dependent B cell maturation and antibody production <jats:italic>in vitro</jats:italic>. However, the role of cTfh cells in neutralizing antibody (nAb) responses in HCV infection remains unclear. Here, we characterized the phenotype and function of cTfh cells and demonstrated the associations of cTfh cells and their subsets with nAb responses in HCV infection. A total of 38 HCV-infected individuals and 28 healthy controls were enrolled from a pool of injection drug users. The frequency and function of blood Tfh cells were analyzed by flow cytometry. The titers and breadths of serum nAbs were measured using HCV pseudo-particle neutralization assays. Herein, we report several key observations. First, HCV infection skewed cTfh toward CXCR3<jats:sup>+</jats:sup> cTfh cell differentiation. Second, the frequency of CXCR3<jats:sup>+</jats:sup> cTfh cells positively correlated with HCV nAb titers and breadths. Third, CXCR3<jats:sup>+</jats:sup> cTfh cells showed higher expression of Tfh-associated molecules (PD-1, ICOS, IL-21, Bcl-6) compared with CXCR3<jats:sup>−</jats:sup> cTfh cells from individuals with HCV infection. Coculture of cTfh cells and autologous memory B cells <jats:italic>in vitro</jats:italic> indicated that CXCR3<jats:sup>+</jats:sup> cTfh cells show a superior ability to support HCV E2-specific B cell expansion compared with CXCR3<jats:sup>−</jats:sup> cTfh cells from individuals with HCV infection. HCV infection skews cTfh cells toward CXCR3-biased Tfh cell differentiation, which positively correlates with the magnitude and breadth of the HCV nAb response. It is our hope that these findings will provide insights for the rational design of a nAb-based HCV vaccine.</jats:p>
作者机构：
[Wang, Siyang; Liu, Zhigang; Liu, Qiaodan; Yao, Jijin] Sun Yat Sen Univ, Phase 1 Clin Trial Ward, Dept Head & Neck Oncol, Canc Ctr,Affiliated Hosp 5, Zhuhai 519001, Peoples R China.;[Zhou, Jiao; Liu, Guiyun; Xu, Chenyang; Liu, Fengzin; Jiang, Rong] Cent S Univ, Xiangya Sch Med, Affiliated Canc Hosp, Dept Radiat Oncol,Hunan Canc Hosp, Changsha 410000, Hunan, Peoples R China.;[Zhou, Jiao; Liu, Guiyun; Xu, Chenyang; Liu, Fengzin; Jiang, Rong] Univ South China, Dept Clin Med, Hengyang 421000, Peoples R China.;[Jiang, Wen] Univ Texas Southwestern Med Ctr Dallas, Dept Radiat Oncol, Dallas, TX 75390 USA.
通讯机构：
[Liu, Zhigang] S;Sun Yat Sen Univ, Phase 1 Clin Trial Ward, Dept Head & Neck Oncol, Canc Ctr,Affiliated Hosp 5, Zhuhai 519001, Peoples R China.
摘要：
Nasopharyngeal carcinoma (NPC) is endemic in southern China. Due to the unique anatomical and biological properties of NPCs, radiotherapy or combined modality based on radiotherapy is an effective treatment option. Helical tomotherapy (HT) is an emerging intensity modulated radiotherapy technology. The advantages of dose homogeneity, steepness of dose gradient, and protection of normal organs are reflected in the treatment of head and neck cancers. We present the preliminary (2-year) clinical outcomes of HT in 85 patients with locally advanced NPC (LA-NPC). Of these patients, 3 patients (3.5%) experienced treatment interruption due to severe pulmonary infection, and 82 (96.5%) completed radiation treatments. The 2-year estimate of progression-free survival, local relapse-free survival, nodal relapse-free survival, distant metastases-free survival, and overall survival rate were 90%, 96.3%, 98.8%, 96.3%, and 96.3%, respectively. Among the three patients that died, one had stage III disease and died from fatal nasopharyngeal bleeding after radiotherapy, while the other two patients succumbed to local recurrence. Our experience suggests that HT can achieve promising disease control and survival in the treatment of LA-NPC patients with mild acute and late toxicity profiles.
摘要：
<jats:title>Abstract</jats:title><jats:sec><jats:title>Aims</jats:title><jats:p>Reactive oxygen species (ROS) play essential roles in the pulmonary vascular remodelling associated with hypoxia-induced pulmonary hypertension (PH). Vascular peroxidase 1 (VPO1) is a newly identified haeme-containing peroxidase that accelerates oxidative stress development in the vasculature. This study aimed to determine the potential role of VPO1 in hypoxia-induced PH-related vascular remodelling.</jats:p></jats:sec><jats:sec><jats:title>Methods and results</jats:title><jats:p>The vascular morphology and VPO1 expression were assessed in the pulmonary arteries of Sprague–Dawley (SD) rats. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 4 (NOX4) and VPO1 expression and HOCl production were significantly increased in hypoxic rats, which also exhibited obvious vascular remodelling. Furthermore, a hypoxia-induced PH model was generated by exposing primary rat pulmonary artery smooth muscle cells (PASMCs) to hypoxic conditions (3% O2, 48 h), which significantly increased the expression of NOX4 and VPO1 and the production of HOCl. These hypoxic changes were accompanied by enhanced proliferation, apoptosis resistance, and migration. In PASMCs, hypoxia-induced changes, including effects on the expression of cell cycle regulators (cyclin B1 and cyclin D1), apoptosis-related proteins (bax, bcl-2, and cleaved caspase-3), migration promoters (matrix metalloproteinases 2 and 9), and NF-κB expression, as well as the production of HOCl, were all inhibited by silencing VPO1 with small interfering RNAs. Moreover, treatment with HOCl under hypoxic conditions upregulated NF-κB expression and enhanced proliferation, apoptosis resistance, and migration in PASMCs, whereas BAY 11-7082 (an inhibitor of NF-κB) significantly inhibited these effects.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>Collectively, these results demonstrate that VPO1 promotes hypoxia-induced proliferation, apoptosis resistance, and migration in PASMCs via the NOX4/VPO1/HOCl/NF-κB signalling pathway.</jats:p></jats:sec>
摘要：
Worldwide, gastric cancer (GC) is one of the deadliest malignant tumors of the digestive system. Moreover, microRNAs (miRNAs) of exosomes harbored within cancer cells have been determined to induce inflammatory conditions that accelerate tumor growth and metastasis. Interestingly, the oncogenic role of bone marrow mesenchymal stem cells (BM-MSCs) in the modulation of immunosuppression, tumor invasion, and metastasis was discovered to be partly mediated through the secretion of exosomes. In this article, high expression of miRNA-221 (miR-221) in exosomes of the peripheral blood was determined to be positively correlated with the poor clinical prognosis of GC, especially with respect to tumor, node, and metastases stage. Therefore, the expression of miR-221 in exosomes of the peripheral blood may be an important detection index for GC. Proliferation, migration, invasion, and adhesion to the matrix of GC BGC-823 and SGC-7901 cells were significantly enhanced by exosomes that originated from BM-MSCs that were transfected with miR-221 mimics. In conclusion, extracted exosomes from BM-MSCs transfected with miR-221 oligonucleotides can act as high-efficiency nanocarriers, which can provide sufficient miR-221 oligonucleotides to influence the tumor microenvironment and tumor aggressiveness effectively. Notably, the use of a miR-221 inhibitor with an excellent restraining effect in exosomes provides therapeutic potential for GC in future clinical medicine.
通讯机构：
[Yimou Wu] I;Institution of Pathogenic Biology, Medical College, University of South China, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hunan Provincial Key Laboratory for Special Pathogens Prevention and Control, University of South China, Hengyang 421001, China
通讯机构：
[Zhuang, T; Wang, H; Zhu, J] X;[Mu, Kun] S;[Zhu, Jian] U;Xinxiang Med Univ, Sch Lab Med, Res Ctr Immunol, Xinxiang, Henan, Peoples R China.;Xinxiang Med Univ, Henan Collaborat Innovat Ctr Mol Diag & Lab Med, Xinxiang, Henan, Peoples R China.
关键词：
estrogen receptor alpha;protein SHARPIN;ubiquitin protein ligase E3;unclassified drug;Article;cancer growth;cancer prognosis;cellular distribution;controlled study;estrogen receptor positive breast cancer;estrogen responsive element;gene expression;human;immunohistochemistry;protein expression;protein function;protein localization;protein protein interaction;protein stability;RNA sequence;signal transduction;ubiquitination
摘要：
Estrogen receptor a is expressed in the majority of breast cancers and promotes estrogen-dependent cancer progression. In our study, we identified the novel E3 ubiquitin ligase SHARPIN function to facilitate ER alpha signaling. SHARPIN is highly expressed in human breast cancer and correlates with ER alpha protein level by immunohistochemistry. SHARPIN expression level correlates with poor prognosis in ER alpha positive breast cancer patients. SHARPIN depletion based RNA-sequence data shows that ER alpha signaling is a potential SHARPIN target. SHARPIN depletion significantly decreases ER alpha protein level, ER alpha target genes expression and estrogen response element activity in breast cancer cells, while SHARPIN overexpression could reverse these effects. SHARPIN depletion significantly decreases estrogen stimulated cell proliferation in breast cancer cells, which effect could be further rescued by ER alpha overexpression. Further mechanistic study reveals that SHARPIN mainly localizes in the cytosol and interacts with ER alpha both in the cytosol and the nuclear. SHARPIN regulates ER alpha signaling through protein stability, not through gene expression. SHARPIN stabilizes ER alpha protein via prohibiting ER alpha protein poly-ubiquitination. Further study shows that SHARPIN could facilitate the mono-ubiquitinaiton of ER alpha at K302/303 sites and facilitate ERE luciferase activity. Together, our findings propose a novel ER alpha modulation mechanism in supporting breast cancer cell growth, in which SHARPIN could be one suitable target for development of novel therapy for ER alpha positive breast cancer.
期刊：
Pathogens and Disease,2017年75(7):188-188 ISSN：0928-8244
通讯作者：
Chen, Lili
作者机构：
[Bai, Qinqin; Zeng, Xindian; Chen, Lili; Zhou, Pufan; Liu, Ziqing; Zhou, Peng; Sun, Yuanbin] Univ South China, Coll Publ Hlth, 28 West Changsheng Rd, Hengyang 421001, Hunan, Peoples R China.;[Chen, Shenghua] Univ South China, Med Coll, 28 West Changsheng Rd, Hengyang 421001, Hunan, Peoples R China.;[Wu, Haiying] Univ South China, Affiliated Hosp 2, 28 West Changsheng Rd, Hengyang 421001, Hunan, Peoples R China.;[Hu, Chunsheng] Hunan Prov Ctr Dis Control & Provent, Outpatient Dept, Changsha 421000, Hunan, Peoples R China.;[Chen, Yuyu] Cent S Univ, Hunan Canc Hosp, Changsha 421000, Hunan, Peoples R China.
通讯机构：
[Chen, Lili] U;Univ South China, Coll Publ Hlth, 28 West Changsheng Rd, Hengyang 421001, Hunan, Peoples R China.
会议名称：
2017年第二届全国特殊病原体学术会议
会议时间：
2017-08-13
会议地点：
南京
会议论文集名称：
2017年第二届全国特殊病原体学术会议论文集
关键词：
Chlamydia psittaci;STAT3;apoptosis;Bax/Bcl-2
摘要：
The Janus kinase-signal transducer and activator of transcription-3 (JAK-STAT3) signaling pathway is a key regulator of cell growth, motility, migration, invasion and apoptosis in mammalian cells. Infection with intracellular pathogens of the genus Chlamydia can inhibit host cell apoptosis, and here we asked whether the JAK-STAT3 pathway participates in chlamydial anti-apoptotic activity. We found that, compared with uninfected cells, levels of JAK1 and STAT3 mRNA as well as total and phosphorylated JAK1 and STAT3 protein were significantly increased in Chlamydia psittaci-infected HeLa cells. Moreover, the apoptosis rate of infected cells was higher after treatment with the tyrosine kinase inhibitor AG-490 (2-cyano-3-(3,4-dihydroxyphenyl)-N-(phenylmethyl)-2-propenamide). Immunoblotting of apoptosis-related proteins showed that C. psittaci infection reduces Bax, but increases Bcl-2, protein levels, resulting in reduced activation of caspase-3, caspase-7, caspase-9 and PARP; AG490 attenuates these effects. Together, our data suggest that the JAK/STAT3 signaling pathway facilitates the anti-apoptotic effect of C. psittaci infection by reducing the Bax/Bcl-2 apoptotic switch ratio, and by inhibiting the intracellular activation of key pro-apoptotic enzymes.
期刊：
Pathogens and Disease,2017年75(9) ISSN：0928-8244
通讯作者：
Chen, Lili
作者机构：
[Bai, Qinqin; Zeng, Xindian; Chen, Lili; Zhou, Pufan; Liu, Ziqing; Zhou, Peng; Sun, Yuanbin] Univ South China, Coll Publ Hlth, 28 West Changsheng Rd, Hengyang 421001, Hunan, Peoples R China.;[Chen, Shenghua] Univ South China, Med Coll, 28 West Changsheng Rd, Hengyang 421001, Hunan, Peoples R China.;[Wu, Haiying] Univ South China, Affiliated Hosp 2, 28 West Changsheng Rd, Hengyang 421001, Hunan, Peoples R China.;[Hu, Chunsheng] Hunan Prov Ctr Dis Control & Provent, Outpatient Dept, Changsha 421000, Hunan, Peoples R China.;[Chen, Yuyu] Cent S Univ, Xiangya Sch Med, Hunan Canc Hosp, Changsha 421000, Hunan, Peoples R China.
通讯机构：
[Chen, Lili] U;Univ South China, Coll Publ Hlth, 28 West Changsheng Rd, Hengyang 421001, Hunan, Peoples R China.
关键词：
Erratum;error;erratum
摘要：
The publisher apologizes that this article was originally published under an incorrect DOI (10.1093/femsle/ftx088). The correct DOI is now displayed.
摘要：
Asthma is a complicated systemic disease of the airways, which is characterized by variable symptoms, including bronchial hyper-responsive ness, inflammation and airflow obstruction. The prevalence of asthma has increased 2-3-fold over recent decades in developed countries; however, the molecular mechanism of asthma remains unclear. In the current study, the expression of recombinant protein Dermatophagoides farinaeI (Derf I) was induced by isopropyl β-D-1-thiogalactoside (IPTG) and purified using Ni-NTA. Derf I, an important antigen of asthma, was used to establish the animal model of asthma. Airway hyper-responsiveness was mea sured using unrestrained whole-body plethysmography with a four-chamber system. Immunoglobulin (Ig)E, IgG and IgG2a were analyzed using indirect enzyme-linked immunosorbent assay (ELISA). Proteomic technology was applied to detect the difference between the normal lung tissue and asthma lung tissue samples of the asthma model. Cytokines in bronchoalveolar lavage fluid and the splenocyte culture medium were measured by ELISA and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was performed to detect the mRNA expression of ATP synthase, H+ transporting, mitochondrial F1 complex, β polypeptide (ATP5b). In addition, cell growth of arterial smooth muscle cells (ASMCs) was evaluated by MTT assay. In the current study, Derf I was successfully used to construct the animal model of asthma. Out of 23 proteins that exhibit 3-fold upregulation or downregulation, ATP5b was chosen for further investigation. The data indicated that ATP5b was.
