المؤلفون: Hao Luo, Qing Li, Ren-Tao Wang, Liang Zhang, Wei Zhang, Meng-Sheng Deng, Yuan-Yuan Luo, Xintong Ji, Yongheng Wen, Xuan-Rui Zhou, Bo Xu, Dong Wang, Bin Hu, Hua Jin, Cheng-Xiong Xu

المصدر: Experimental Hematology & Oncology, Vol 12, Iss 1, Pp 1-17 (2023)

مصطلحات موضوعية: Recurrence, Early-stage NSCLC, Pro-SFTPB, PGK1, Akt pathway, Diseases of the blood and blood-forming organs, RC633-647.5, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282

الوصف: Abstract Recurrence is one of the main causes of treatment failure in early-stage non-small cell lung cancer (NSCLC). However, there are no predictors of the recurrence of early-stage NSCLC, and the molecular mechanism of its recurrence is not clear. In this study, we used clinical sample analysis to demonstrate that low levels of expression of precursor surfactant protein B (pro-SFTPB) in primary NSCLC tissue compared to their adjacent tissues are closely correlated with recurrence and poor prognosis in early-stage NSCLC patients. In vitro and in vivo experiments showed that downregulation of pro-SFTPB expression activates the Akt pathway by upregulating PGK1, which promotes metastasis and tumorigenicity in NSCLC cells. We then demonstrated that pro-SFTPB suppresses the formation of the ADRM1/hRpn2/UCH37 complex by binding to ADRM1, which inhibits PGK1 deubiquitination, thus accelerating ubiquitin-mediated PGK1 degradation. In summary, our findings indicate that low expression of pro-SFTPB in primary NSCLC compared to their adjacent tissue has potential as a predictor of recurrence and poor prognosis in early-stage NSCLC. Mechanistically, downregulation of pro-SFTPB attenuates inhibition of ADRM1-deubiquitinated PGK1, resulting in elevated levels of PGK1 protein; this activates the Akt pathway, ultimately leading to the progression of early-stage NSCLC.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2162-3619Test

الوصول الحر: https://doaj.org/article/58deed27543349ada6fd8a9eb430d987Test

المؤلفون: Qing Li, Hao Luo, Fu‐Qiang Dai, Ren‐Tao Wang, Xiao‐Qing Fan, Yuan‐Yuan Luo, Meng‐Sheng Deng, Yulun Wang, Tan Long, Wei Guo, Bo Xu, Cheng‐Xiong Xu, Hua Jin

المصدر: Advanced Science, Vol 10, Iss 11, Pp n/a-n/a (2023)

مصطلحات موضوعية: esophageal squamous cell carcinoma recurrence, myosin‐9, sterile alpha motif domain‐containing protein 9, β‐catenin signaling, Science

الوصف: Abstract Recurrence is a challenge to survival after the initial treatment of esophageal squamous cell carcinoma (ESCC). But, its mechanism remains elusive and there are currently no biomarkers to predict postoperative recurrence. Here, the possibility of sterile alpha motif domain‐containing protein 9 (SAMD9) as a predictor of postoperative recurrence of ESCC is evaluated and the molecular mechanisms by which SAMD9 promotes ESCC recurrence are elucidated. The authors found that the high level of SAMD9 is correlated with postoperative recurrence and poor prognosis of ESCC. Overexpression of SAMD9 promotes tumor stemness, angiogenesis, and EMT, while downregulation of SAMD9 reduced these phenotypes. Mechanistically, it is found that SAMD9 stimulated ubiquitination‐mediated glycogen synthase kinase‐3 beta (GSK‐3β) degradation by interaction with myosin‐9 (MYH9) and TNF receptor‐associated factor 6 (TRAF6), which in turn activated Wnt/β‐catenin pathway. Further, the authors demonstrated that silencing SAMD9 inhibited lung metastasis and tumor formation in vivo. Finally, the authors found that silencing MYH9 or β‐catenin, or overexpressing GSK‐3β inhibited SAMD9‐stimulated ESCC cell stemness, EMT, angiogenesis, metastasis, and tumorigenicity. Together, the findings indicate that the SAMD9/MYH9/GSK3β/β‐catenin axis promotes ESCC postoperative recurrence and that SAMD9 is a crucial target for ESCC therapy. Additionally, SAMD9 has the potential as a predictor of postoperative recurrence in ESCC.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2198-3844Test

الوصول الحر: https://doaj.org/article/9223b7359de3419eba1e03fd7b3217fcTest

المؤلفون: Guo‐Bing Qiao, Ren‐Tao Wang, Shu‐Nan Wang, Shao‐Lin Tao, Qun‐You Tan, Hua Jin

المصدر: Thoracic Cancer, Vol 12, Iss 10, Pp 1558-1569 (2021)

مصطلحات موضوعية: GRP75, HMGA1, recurrence, stage I LUAD, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282

الوصف: Abstract Background Recurrence is a major challenge in early‐stage lung adenocarcinoma (LUAD) treatment. Here, we investigated the role and mechanism of high‐mobility group AT‐hook 1 (HMGA1) and glucose‐regulated protein 75‐kDa (GRP75) in stage I LUAD and evaluated their potential as biomarkers for predicting the recurrence and prognosis of stage I LUAD. Methods The TCGA dataset was used to investigate the clinical significance of HMGA1 and GRP75 in early‐stage LUAD. The biological functions of HMGA1 and GRP75 in LUAD were investigated both in vitro and in vivo through overexpression and knockdown experiments. The interaction and regulation between HMGA1 and GRP75 were evaluated with coimmunoprecipitation and ubiquitination assays. The downstream signaling pathway of the GRP75/HMGA1 axis was investigated by mRNA‐sequencing analysis. Results Both HMGA1 expression levels and GRP75 expression levels were associated with recurrence in stage I LUAD patients. In particular, HMGA1 had potential as an independent prognostic factor in stage I LUAD patients. Overexpression of GRP75 or HMGA1 significantly stimulated LUAD cell growth and metastasis, while silencing GRP75 or HMGA1 inhibited LUAD cell growth and metastasis in vitro and in vivo. Importantly, GRP75 inhibited ubiquitination‐mediated HMGA1 degradation by directly binding to HMGA1, thereby causes HMGA1 upregulation in LUAD. In addition, the GRP75/HMGA1 axis played its role by activating JNK/c‐JUN signaling in LUAD. Conclusions The activation of GRP75/HMGA1/JNK/c‐JUN signaling is an important mechanism that promotes the progression of stage I LUAD, and a high level of HMGA1 is a novel biomarker for predicting recurrence and a poor prognosis in stage I LUAD patients.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/1759-7706Test; https://doaj.org/toc/1759-7714Test

الوصول الحر: https://doaj.org/article/bb600436080644e8bacb7f435a440ffaTest

المؤلفون: Fu-Qiang Dai, Cheng-Run Li, Xiao-Qing Fan, Long Tan, Ren-Tao Wang, Hua Jin

المصدر: Molecular Therapy: Nucleic Acids, Vol 16, Iss , Pp 675-685 (2019)

مصطلحات موضوعية: Therapeutics. Pharmacology, RM1-950

الوصف: Dysregulated microRNAs (miRNAs) play crucial roles in the regulation of cancer stem cells (CSCs), and CSCs are closely associated with tumor initiation, metastasis, and recurrence. Here we found that miR-150-5p was significantly downregulated in CSCs of non-small-cell lung cancer (NSCLC) and its expression level was negatively correlated with disease progression and poor survival in patients with NSCLC. Inhibition of miR-150-5p increased the CSC population and sphere formation of NSCLC cells in vitro and stimulated NSCLC cell tumorigenicity and metastatic colonization in vivo. In contrast, miR-150-5p overexpression potently inhibited sphere-formed NSCLC cell tumor formation, metastatic colonization, and recurrence in xenograft models. Furthermore, we identified that miR-150-5p significantly inhibited wingless (Wnt)-β-catenin signaling by simultaneously targeting glycogen synthase kinase 3 beta interacting protein (GSKIP) and β-catenin in NSCLC cells. miR-150-5p also targeted high mobility group AT-hook 2 (HMGA2), another regulator of CSCs, and Wnt-β-catenin signaling. The restoration of HMGA2 and β-catenin blocked miR-150-5p overexpression-induced inhibition of CSC traits in NSCLC cells. These findings suggest that miR-150-5p functions as a CSC suppressor and that overexpression of miR-150-5p may be a novel strategy to inhibit CSC-induced metastasis and recurrence in NSCLC. Keywords: miR-150-5p, cancer stem cell, metastasis, recurrence, NSCLC

وصف الملف: electronic resource

العلاقة: http://www.sciencedirect.com/science/article/pii/S2162253119300903Test; https://doaj.org/toc/2162-2531Test

الوصول الحر: https://doaj.org/article/4d08c83c685f403385e629d9555d55faTest

المؤلفون: Hua Jin, Qing Li, Fenghao Cao, Shu-Nan Wang, Ren-Tao Wang, Yun Wang, Qun-You Tan, Cheng-Run Li, Hua Zou, Dong Wang, Cheng-Xiong Xu

المصدر: Molecular Therapy: Nucleic Acids, Vol 9, Iss C, Pp 145-154 (2017)

مصطلحات موضوعية: lung cancer, miR-124, Akt activation, NNK-induced lung cancer, K-ras mutation-induced lung tumorigenesis, Therapeutics. Pharmacology, RM1-950

الوصف: Dysregulated miRNAs play important role in K-ras mutation or smoking caused lung tumorigenesis. Here, we investigate the role and mechanism of miR-124 in K-ras mutation or smoking-caused lung tumorigenesis and evaluate the therapeutic potential of miR-124 agomiR in K-ras mutation or smoking-caused lung cancer treatment. Our data show that smoking suppresses miR-124 expression, and decreased miR-124 expression is inversely correlated with the p-Akt level and predicts poor overall survival in non-small-cell lung cancer (NSCLC) patients. The overexpression of miR-124 suppressed NSCLC growth by inhibiting the Akt pathway by targeting Akt1 and Akt2. In addition, the systemic delivery of miR-124 agomiR dramatically suppressed tumorigenesis in both NNK-induced lung cancer model and K-rasLA1 transgenic mice by increasing apoptosis and inhibiting cell proliferation. Our findings suggest that smoking inhibits the expression of miR-124, and decreased miR-124 contributes to Akt activation, thereby promoting NSCLC progression. Our findings also represent a novel potential therapeutic strategy for lung cancer.

وصف الملف: electronic resource

العلاقة: http://www.sciencedirect.com/science/article/pii/S216225311730255XTest; https://doaj.org/toc/2162-2531Test

الوصول الحر: https://doaj.org/article/3bdf04390aa74de0be244bcdbeedc076Test

المؤلفون: Fei Qi, Guo-Xin Zhang, Dan-Yang She, Zhi-Xin Liang, Ren-Tao Wang, Zhen Yang, Liang-An Chen, Jun-Chang Cui

المصدر: Chinese Medical Journal, Vol 128, Iss 20, Pp 2707-2713 (2015)

مصطلحات موضوعية: Acinetobacter Baumannii, Antibiotic Resistance, Community-acquired Pneumonia, CURB-65, Healthcare-associated Pneumonia, Pseudomonas Aeruginosa, Medicine

الوصف: Background: Healthcare-associated pneumonia (HCAP) is associated with drug-resistant pathogens and high mortality, and there is no clear evidence that this is due to inappropriate antibiotic therapy. This study was to elucidate the clinical features, pathogens, therapy, and outcomes of HCAP, and to clarify the risk factors for drug-resistant pathogens and prognosis. Methods: Retrospective observational study among hospitalized patients with HCAP over 10 years. The primary outcome was 30-day all-cause hospital mortality after admission. Demographics (age, gender, clinical features, and comorbidities), dates of admission, discharge and/or death, hospitalization costs, microbiological results, chest imaging studies, and CURB-65 were analyzed. Antibiotics, admission to Intensive Care Unit (ICU), mechanical ventilation, and pneumonia prognosis were recorded. Patients were dichotomized based on CURB-65 (low- vs. high-risk). Results: Among 612 patients (mean age of 70.7 years), 88.4% had at least one comorbidity. Commonly detected pathogens were Acinetobacter baumannii, Pseudomonas aeruginosa, and coagulase-negative staphylococci. Initial monotherapy with β-lactam antibiotics was the most common initial therapy (50%). Mean age, length of stay, hospitalization expenses, ICU admission, mechanical ventilation use, malignancies, and detection rate for P. aeruginosa, and Staphylococcus aureus were higher in the high-risk group compared with the low-risk group. CURB-65 ≥3, malignancies, and mechanical ventilation were associated with an increased mortality. Logistic regression analysis showed that cerebrovascular diseases and being bedridden were independent risk factors for HCAP. Conclusion: Initial treatment of HCAP with broad-spectrum antibiotics could be an appropriate approach. CURB-65 ≥3, malignancies, and mechanical ventilation may result in an increased mortality.

وصف الملف: electronic resource

العلاقة: http://www.cmj.org/article.asp?issn=0366-6999;year=2015;volume=128;issue=20;spage=2707;epage=2713;aulast=QiTest; https://doaj.org/toc/0366-6999Test

الوصول الحر: https://doaj.org/article/70f89078f4c24956830a18272f7c3a2cTest

المؤلفون: Hao Luo, Qing Li, Ren-Tao Wang, Liang Zhang, Wei Zhang, Meng-Sheng Deng, Yuan-Yuan Luo, Xintong Ji, Yongheng Wen, Xuan-Rui Zhou, Bo Xu, Dong Wang, Bin Hu, Hua Jin, Cheng-Xiong Xu

مصطلحات موضوعية: Biophysics, Biochemistry, Cell Biology, Molecular Biology, Pharmacology, Developmental Biology, Cancer, Inorganic Chemistry, Plant Biology, Physical Sciences not elsewhere classified, Recurrence, Early-stage NSCLC, Pro-SFTPB, PGK1, Akt pathway

الوصف: Additional file 1: Fig. S1 RNA sequencing analysis. a Heatmap showing differentially expressed genes between primary tumors of stage I lung adenocarcinoma patients with postoperative metastatic recurrence and those with no recurrence. RNA sequencing was performed using primary tumors from stage I lung adenocarcinoma patients who experienced metastatic recurrence within 24 months after the operation (n=7) and from patients who experienced no recurrence within 60 months after the operation (n=7). b Genes whose expression was significantly increased in primary tumors from stage I lung adenocarcinoma patients who had not relapsed within 24 months relative to those who had relapsed within 60 months. Fig. S2 Measurement of pro-SFTPB expression in normal lung epithelial cells and NSCLC cell lines by Western blotting. HPA-EpiC, human pulmonary alveolar epithelial cell. Fig. S3 Overexpression of pro-SFTPB inhibited NSCLC progression in animal models. a Vector or pro-SFTPB expression plasmid was transfected into H460 cells. The expression level of pro-SFTPB was measured by Western blot in normal lung epithelial cells and H460 cells that transfected with vector or pro-SFTPB expression plasmid (after 72 hs of transfection). b Subcutaneous xenograft model experiment (n=5/group) showing that overexpression of pro-SFTPB inhibited tumor growth. Subcutaneously inject 1 × 107 H460 cells in 1ml PBS into the back of each nude mouse. Tumors were collected and weighted after 1 month of cell injection. (c) Lung metastasis analysis showing that overexpression of pro-SFTPB expression inhibited tumor metastasis (n=5/group). 1 × 107 H460 cells in 1ml PBS injected into each nude mouse through the tail vein. The lungs were collected after one month of cell injection, and counted the number of tumor on the surface of the lungs. Fig. S4 Measurement of PGK1 expression by Western blotting. H1299 and PC-9 cells were transfected with siRNAs against PGK1. The cells were subjected to Western blotting 72 h after transfection. Table S1. Proteins ...

العلاقة: https://figshare.com/articles/journal_contribution/Additional_file_1_of_Downregulation_of_pro-surfactant_protein_B_contributes_to_the_recurrence_of_early-stage_non-small_cell_lung_cancer_by_activating_PGK1-mediated_Akt_signaling/24540652Test

الإتاحة: https://doi.org/10.6084/m9.figshare.24540652.v1Test
https://figshare.com/articles/journal_contribution/Additional_file_1_of_Downregulation_of_pro-surfactant_protein_B_contributes_to_the_recurrence_of_early-stage_non-small_cell_lung_cancer_by_activating_PGK1-mediated_Akt_signaling/24540652Test

المؤلفون: Hua Jin, Zhi-Gang Song, Cheng-Xiong Xu, Meng Xu, Ren-Tao Wang

الوصف: Purpose: The aim of the present study is to investigate the role and mechanism of miR216a in non–small-cell lung cancer (NSCLC).Experimental Design: The expression of miR216a in NSCLC cell lines and from NSCLC patient specimens was measured by real-time qRT-PCR. The correlation between gene expression and patient survival was analyzed using Kaplan–Meier methods. The effects of miR216a on NSCLC cell growth and metastasis were examined both in vitro and in vivo by overexpressing or inhibiting miR216a. Finally, the effect of miR216a on chemoresistance was investigated by MTT assay and flow cytometry.Results: miR216a expression was downregulated in specimens from patients with NSCLC compared with corresponding nontumor lung tissues. Clinical data indicate that decreased miR216a expression is inversely correlated with cancer stage, metastasis, and poor survival in patients with NSCLC. Our data also show that overexpression of miR216a suppresses NSCLC cell growth and metastasis, and enhances cisplatin-induced cell growth inhibition and apoptosis. In contrast, inhibition of miR216a stimulates NSCLC cell growth and metastasis, and suppresses cisplatin-induced cell growth inhibition and apoptosis. Furthermore, we demonstrate that miR216a exerts its role by directly targeting eIF4B and ZEB1.Conclusion: Our findings suggest that miR216a is a cancer suppressor miRNA and that overexpression of miR216a is a novel NSCLC treatment strategy. In addition, our clinical data indicate that miR216a may be a useful biomarker for predicting NSCLC progression. Clin Cancer Res; 20(17); 4705–16. ©2014 AACR.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::656c1924a67fe1b2c616406e3f08aa8bTest
https://doi.org/10.1158/1078-0432.c.6522774Test

المؤلفون: Hua Jin, Zhi-Gang Song, Cheng-Xiong Xu, Meng Xu, Ren-Tao Wang

الوصف: Supplementary Figure 1. miR-216a negatively regulates non-small cell lung cancer cell growth. Supplementary Figure 2. miR-216a induces apoptosis in vitro and in vivo. Supplementary Figure 3. miR-216a inhibits EMT in non-small cell lung cancer cell. Supplementary Figure 4. Anti-Argonaute 2 RIP-Chip assay shows that overexpression of miR-216a increased Ago2 complex and ZEB1/eIF4B mRNA interaction. Supplementary Figure 5. Correlation of ZEB1/eIF4B expression and miR-216a expression or non-small cell lung cancer (NSCLC) patients' survival. Supplementary Figure 6. Effects of miR-216a on putative target genes expression in A549 and HepG2 cells. Supplementary Figure 7. Expression of miR-216a, ZEB1 and eIF4B. A549 cells were tranfected with indicated plasmid.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::09bb796ccac9b544fde5842b6710e603Test
https://doi.org/10.1158/1078-0432.22454529Test

المؤلفون: Qing Li, Hao Luo, Fu‐Qiang Dai, Ren‐Tao Wang, Xiao‐Qing Fan, Yuan‐Yuan Luo, Meng‐Sheng Deng, Yulun Wang, Tan Long, Wei Guo, Bo Xu, Cheng‐Xiong Xu, Hua Jin

المصدر: Advanced Science. 10

مصطلحات موضوعية: General Chemical Engineering, General Engineering, General Physics and Astronomy, Medicine (miscellaneous), General Materials Science, Biochemistry, Genetics and Molecular Biology (miscellaneous)

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::9345ed47184f34c9a629b44c077fad36Test
https://doi.org/10.1002/advs.202203573Test