31 results on '"Xin Ran"'
Search Results
2. Corrigendum to 'NFAT1 hypermethylation promotes epithelial‐mesenchymal transition and metastasis in nasopharyngeal carcinoma by activating ITGA6 transcription' [Neoplasia 21 (2019): 311–321]
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Yuan Lei, Xiao-Hong Hong, Na Liu, Ying-Qin Li, Pan-Pan Zhang, Jian Zhang, Yawei Yuan, Xiao-Jing Yang, Ya-Qin Wang, Xin Wen, Jun Ma, Ying Sun, Qingmei He, Zi-Qi Zheng, and Xin-Ran Tang
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Transcriptional Activation ,Cancer Research ,Epithelial-Mesenchymal Transition ,Integrin alpha6 ,Epigenesis, Genetic ,Metastasis ,Transcription (biology) ,Cell Line, Tumor ,medicine ,Humans ,Epithelial–mesenchymal transition ,RC254-282 ,Neoplasm Staging ,Nasopharyngeal Carcinoma ,NFATC Transcription Factors ,business.industry ,Gene Expression Profiling ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,DNA Methylation ,medicine.disease ,Gene Expression Regulation, Neoplastic ,Nasopharyngeal carcinoma ,Lymphatic Metastasis ,DNA methylation ,Cancer research ,RNA Interference ,Corrigendum ,Transcriptome ,business ,ITGA6 - Abstract
DNA methylation is an important epigenetic change in carcinogenesis. However, the function and mechanism of DNA methylation dysregulation in nasopharyngeal carcinoma (NPC) is still largely unclear. Our previous genome-wide microarray data showed that NFAT1 is one of the most hypermethylated transcription factor genes in NPC tissues. Here, we found that NFAT1 hypermethylation contributes to its down-regulation in NPC. NFAT1 overexpression inhibited cell migration, invasion, and epithelial-mesenchymal transition in vitro and tumor metastasis in vivo. We further established that the tumor suppressor effect of NFAT1 is mediated by its inactivation of ITGA6 transcription. Our findings suggest the significance of activating NFAT1/ITGA6 signaling in aggressive NPC, defining a novel critical signaling mechanism that drives NPC invasion and metastasis and providing a novel target for future personalized therapy.
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- 2021
3. YPEL3 suppresses epithelial–mesenchymal transition and metastasis of nasopharyngeal carcinoma cells through the Wnt/β-catenin signaling pathway
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Zhang, Jian, Wen, Xin, Ren, Xian-Yue, Li, Ying-Qin, Tang, Xin-Ran, Wang, Ya-Qin, He, Qing-Mei, Yang, Xiao-Jing, Sun, Ying, Liu, Na, and Ma, Jun
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- 2016
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4. Hypermethylation of SHISA3 Promotes Nasopharyngeal Carcinoma Metastasis by Reducing SGSM1 Stability
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Xiao-Jing Yang, Ying Sun, Yuan Lei, Rui Guo, Na Liu, Xin-Ran Tang, Pan Pan Zhang, Ya Qin Wang, Xin Wen, Ying Qin Li, Xiao Hong Hong, Jian Zhang, Jun Ma, and Qing Mei He
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0301 basic medicine ,Regulation of gene expression ,Cancer Research ,biology ,Cell migration ,Methylation ,medicine.disease ,Ubiquitin ligase ,Metastasis ,stomatognathic diseases ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Oncology ,Nasopharyngeal carcinoma ,030220 oncology & carcinogenesis ,DNA methylation ,otorhinolaryngologic diseases ,biology.protein ,Cancer research ,medicine ,Small G protein signaling modulator 1 - Abstract
Altered DNA methylation is a key feature of cancer, and aberrant methylation is important in nasopharyngeal carcinoma (NPC) development. However, the methylation mechanisms underlying metastasis of NPC remain unclear. Analyzing data from public databases and conducting our own experiments, we report here that promoter hypermethylation of SHISA3 is common and contributes to the downregulation of this gene in many types of tumors, including NPC. SHISA3 suppressed NPC cell invasion and metastasis in vitro and in vivo by impeding the E3 ubiquitin ligase tripartite motif containing 21 (TRIM21)–mediated ubiquitination and degradation small G protein signaling modulator 1 (SGSM1) and by inhibiting the MAPK pathway activation. Silencing SGSM1 abrogated the inhibitory effect of SHISA3 on NPC cell migration and invasion. This newly identified SHISA3–TRIM21–SGSM1 axis could be a novel therapeutic target in NPC. Significance: These findings highlight the mechanism by which a newly identified tumor suppressor SHISA3 suppresses invasion and metastasis of nasopharyngeal carcinoma.
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- 2019
5. The biological functions of LGR5 in promoting non-small cell lung cancer progression
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Gao, Fei, Xu, Jun-Chi, You, Xin-Ran, Gao, Xin, Wei, Jia-Ling, Li, Shu-Xiang, Zhu, Chen-Lu, and Yang, Chen
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non-small cell lung cancer (NSCLC) ,Cancer Research ,Oncology ,Proliferation ,metastasis ,Original Article ,Radiology, Nuclear Medicine and imaging ,invasion ,respiratory tract diseases ,leucine-rich repeat-containing G-protein-coupled receptor 5 (LGR5) - Abstract
Background The Leucine-rich repeat-containing G-protein-coupled receptor 5 (LGR5), which is used as a marker of adult stem cells and colorectal cancer stem cells (CSCs), is closely associated with the progression of non-small cell lung cancer (NSCLC). This study aimed to identify the clinical significance and biological function of LGR5 in NSCLC. Methods Quantitative reverse transcription polymerase chain reaction (RT-PCR) was applied to detect the expression of LGR5 and stemness-related genes in 22 NSCLC patients, and the clinical significance of LGR5 in NSCLC progression was estimated by statistical analysis. LGR5 overexpressing A549- and H1299-transfected cells were established, and CCK-8 and clone formation assays were used to test the proliferation ability. A wound-healing assay was utilized to clarify the migration ability. The invasion ability was confirmed via the Transwell assay kit. Results LGR5 expression was markedly higher in NSCLC tissues than in the matched adjacent normal tissues, and had a trend to associate with tumor size, lymph node metastasis, and TNM stage. The proliferation rates, clone formation rates, wound healing rates, number of invasive cells, and the NOTCH1 expression of the LGR5 overexpressing groups, were significantly higher than those of the control groups. Conclusions LGR5 plays an essential role in NSCLC tumorigenesis and is closely associated with the proliferation, metastasis, and invasion of NSCLC cells. LGR5 may promote NSCLC progression via NOTCH1 and could be a new target for gene-targeted therapies for NSCLC.
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- 2019
6. Clinical Significance of B7-H3 Expression During the Progression of Hepatitis B Virus Infection
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Ping Xu, Jun-Chi Xu, Chuan-Wu Zhu, Chen-Lu Zhu, Li Zhu, Xiao-Yan Zhu, Xin-Ran You, Shuxiang Li, Hui Chen, Chen Yang, and Fei Gao
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Male ,0301 basic medicine ,Hepatitis B virus ,B7 Antigens ,Carcinoma, Hepatocellular ,Cirrhosis ,Immunology ,Kaplan-Meier Estimate ,medicine.disease_cause ,T-Lymphocytes, Regulatory ,Flow cytometry ,Metastasis ,03 medical and health sciences ,Hepatitis B, Chronic ,0302 clinical medicine ,Liver Function Tests ,Downregulation and upregulation ,Virology ,medicine ,Humans ,Clinical significance ,Aspartate Aminotransferases ,medicine.diagnostic_test ,business.industry ,Liver Neoplasms ,Alanine Transaminase ,Middle Aged ,Prognosis ,medicine.disease ,Progression-Free Survival ,digestive system diseases ,Up-Regulation ,030104 developmental biology ,Liver ,030220 oncology & carcinogenesis ,Hepatocellular carcinoma ,Disease Progression ,Molecular Medicine ,Immunohistochemistry ,Female ,business ,Follow-Up Studies ,T-Lymphocytes, Cytotoxic - Abstract
B7-H3, one of the costimulatory members participating in checkpoint pathway, has been shown to be upregulated after hepatitis B virus (HBV) infection. To further explore the clinical significance of dynamic B7-H3 expression during the progression of HBV infection, we systematically investigated the expression pattern of B7-H3 and the correlation of B7-H3 expression with the ratio of T lymphocyte subsets and clinical parameters at different stages in the course of the disease. Flow cytometry and enzyme-linked immunosorbent assay data showed that soluble form of B7-H3 (sB7-H3) was positively correlated with the frequency of Treg cells in acute hepatitis B (AHB), chronic hepatitis B (CHB), and hepatocellular carcinoma patients with HBV infection (HBV-HCC). Membrane form of B7-H3 (mB7-H3) expressed on Treg cells and monocytes was positively correlated with the frequency of Treg cells in CHB. SB7-H3 had relationship with mB7-H3 expressed on Treg cells and monocytes at different stages during HBV infection, except for HBV-HCC. MB7-H3 expressed on Treg cells was positively correlated with that on monocytes in AHB, CHB, HBV-liver cirrhosis, and HBV-HCC. The B7-H3 expression was positively correlated with aspartate aminotransferase and alanine aminotransferase levels in CHB and sB7-H3 level was higher in late tumor/node/metastasis (TNM) stage in HCC. Higher mB7-H3 expression was associated with greater tumor size, later TNM stage, and worse prognosis in HBV-HCC indicated by immunohistochemistry. Taken together, these results suggested that B7-H3 might contribute to the progression of HBV infection by triggering inhibitory signals in effector T cells and it was closely associated with the progression and poor prognosis during HBV infection. B7-H3 could be utilized as a potential clinical indicator and a potential target for therapeutic strategies against HBV infection.
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- 2018
7. Integrative evaluation of primary and metastatic lesion spectrum to guide anti-PD-L1 therapy of non-small cell lung cancer: results from two randomized studies
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Xue Bai, Zhong-Yi Dong, Xin-Ran Tang, Si-Cong Ma, Hong-Bo Zhu, Dehua Wu, Jian-Guo Zhou, Zhi-Jiao Duan, Jian Wang, Li-Li Long, Xue-Jun Guo, Yan-Pei Zhang, Ze-Qin Guo, and Qiang John Fu
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0301 basic medicine ,Oncology ,medicine.medical_specialty ,Lung Neoplasms ,medicine.medical_treatment ,Immunology ,Docetaxel ,Metastasis ,03 medical and health sciences ,0302 clinical medicine ,Non-small cell lung cancer ,Atezolizumab ,Carcinoma, Non-Small-Cell Lung ,Internal medicine ,organ ,medicine ,metastasis ,Humans ,Immunology and Allergy ,Lung cancer ,RC254-282 ,Original Research ,Retrospective Studies ,Chemotherapy ,business.industry ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Antibodies, Monoclonal ,Immunotherapy ,RC581-607 ,medicine.disease ,Blockade ,030104 developmental biology ,030220 oncology & carcinogenesis ,Cohort ,immunotherapy ,Immunologic diseases. Allergy ,business ,tumor burden ,Research Article ,medicine.drug - Abstract
Objectives: Clinical benefits of immune-checkpoint blockade (ICB) versus standard chemotherapy have been established in unselected non-small cell lung cancer (NSCLC). However, the response to ICB therapy among patients is heterogeneous in clinical practice. Materials and Methods: We retrospectively assessed the predicitive effect of the primary and metastatic lesion spectrum (baseline sum of the longest diameters [SLD], number of metastatic sites and specific organ metastases) on the efficacy of atezolizumab over docetaxel in OAK and POPLAR trial cohorts. A decision model, termed DSO (Diameter-Site-Organ), based on the spectrum was developed and validated for guiding ICB. Results: Higher SLD (>38 mm) and more metastatic sites (≥2) were characterized with pronounced overall survival (OS) benefits from atezolizumab versus docetaxel. Specifically, adrenal gland and brain metastases were identified as favorable predictors of atezolizumab treatment. The DSO model was developed in the discovery cohort to integrate the directive effect of the primary and metastatic lesion spectrum. Remarkably, a general pattern of enhanced efficacy of atezolizumab versus docetaxel was observed along with the increase of the DSO score. For patients with DSO score > 0, atezolizumab yielded a significantly prolonged OS than docetaxel, whereas OS was generally similar between two treatments in patients with DSO score ≤ 0. Equivalent findings were also seen in the internal and external validation cohorts. Conclusions: The response to anti-PD-L1 therapy among patients varied with the primary and metastatic lesion spectrum. The DSO-based system might provide promising medication guidance for ICB treatment in NSCLC patients.
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- 2021
8. The Islanding effect - a special method of percutaneous peritumor ethanol injection for hepatocellular carcinoma: 15-year follow-up outcome
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Xin-Ran Cai, Ze-Wu Meng, Yan-Ling Chen, Song Liu, and Chang-Zhao Lin
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Male ,medicine.medical_specialty ,Percutaneous ,Carcinoma, Hepatocellular ,recurrence ,medicine.medical_treatment ,Urology ,Observational Study ,Injections, Intralesional ,survival ,Metastasis ,03 medical and health sciences ,percutaneous peritumor ethanol injection ,0302 clinical medicine ,Text mining ,medicine ,Carcinoma ,Humans ,030212 general & internal medicine ,Adverse effect ,prognostic factor ,Aged ,Ethanol ,business.industry ,Liver Neoplasms ,General Medicine ,hepatocellular carcinoma ,Middle Aged ,Ablation ,medicine.disease ,030220 oncology & carcinogenesis ,Hepatocellular carcinoma ,Female ,Percutaneous ethanol injection ,business ,Follow-Up Studies ,Research Article - Abstract
Percutaneous ethanol injection is a well-known ablation therapy for hepatocellular carcinoma and is well-tolerated, inexpensive, and effective with few adverse events. In this study, another type of ethanol injection was introduced in the present study. Sixty two patients with hepatocellular carcinoma received 133 percutaneous peritumor ethanol injection treatments and the 15-year follow-up outcomes were analyzed through a collected database. The technical efficiency was 89.5% (119/133 treatments) after the first percutaneous peritumor ethanol injection procedure. However, after the second repeated percutaneous peritumor ethanol injection procedure, technical efficiency increased to 98.5% (131/133 treatments). The 1 year, 3 years, 5 years, 10 years, and 15 years rates of tumor recurrence were 12.9%, 50.0%, 59.7%, 74.2%, and 74.2%, respectively. Multivariate analysis demonstrated that diabetes, Child–Pugh class B, and tumor size greater than 2 cm were significantly related to tumor recurrence. The 1 year, 3 years, 5 years, 10 years, and 15 years rates of overall survival were 98.4%, 83.6%, 61.3%, 19.4%, and 0%, respectively. Multivariate analysis demonstrated that Child–Pugh class B, tumor size greater than 2 cm, and multiple tumors were significantly related to overall survival. Compared with other ablation methods (including peritumor ethanol injection), percutaneous peritumor ethanol injection can avoid tumor ruptures, reduce tumor proliferation and metastasis, and is suitable for the treatment of small tumors. In addition, when combined with other treatment methods, percutaneous peritumor ethanol injection can form a tumor metastatic isolation zone in advance and improve the comprehensive treatment effect.
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- 2020
9. TIPE3 hypermethylation correlates with worse prognosis and promotes tumor progression in nasopharyngeal carcinoma
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Xian Yue Ren, Jian Zhang, Pan Pan Zhang, Na Liu, Xin-Ran Tang, Ying Qing Li, Ya Qin Wang, Bin Cheng, Xin Wen, Xiao Zhong Chen, Xiao-Jing Yang, Jun Ma, and Qing Mei He
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Male ,0301 basic medicine ,Cancer Research ,Proliferation ,Kaplan-Meier Estimate ,Metastasis ,TIPE3 ,0302 clinical medicine ,Medicine ,Neoplasm Metastasis ,Nasopharyngeal Carcinoma ,Intracellular Signaling Peptides and Proteins ,Methylation ,Middle Aged ,Prognosis ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Gene Expression Regulation, Neoplastic ,Oncology ,CpG site ,030220 oncology & carcinogenesis ,DNA methylation ,Disease Progression ,Female ,Adult ,lcsh:RC254-282 ,Disease-Free Survival ,03 medical and health sciences ,Downregulation and upregulation ,Cell Line, Tumor ,Biomarkers, Tumor ,otorhinolaryngologic diseases ,Humans ,Gene silencing ,Aged ,Cell Proliferation ,business.industry ,Research ,Carcinoma ,Nasopharyngeal Neoplasms ,DNA Methylation ,medicine.disease ,Xenograft Model Antitumor Assays ,stomatognathic diseases ,030104 developmental biology ,Nasopharyngeal carcinoma ,Tumor progression ,Cancer research ,CpG Islands ,business - Abstract
Background Increasing evidence recognizes that DNA methylation abnormalities play critical roles in cancer development. Our previous genome-wide methylation profile showed that tumor necrosis factor-alpha-induced protein 8 like 3 (TIPE3) was hypermethylated in nasopharyngeal carcinoma (NPC). However, the relationship between TIPE3 methylation and its mRNA expression, as well as its biological roles in NPC are unknown. Methods Bisulfite pyrosequencing and quantitative RT-PCR were performed to quantify the TIPE3 methylation and expression levels. Kaplan-Meier curves and Cox regression analysis were used to estimate the correlation between TIPE3 methylation levels and survival in two patient cohorts collected from two hospitals (n = 441). The MTT, colony formation, Transwell migration and invasion assays, and xenograft tumor growth and lung metastatic colonization models were used to identify the functions of TIPE3 on NPC cells. Results We found that TIPE3 CpG island (CGI) was hypermethylated and its mRNA levels were downregulated in many cancers, including NPC. TIPE3 downregulation was associated with its CGI hypermethylation. Furthermore, NPC patients with high TIPE3 CGI methylation levels had poorer clinical outcomes than those with low methylation levels. The TIPE3 CGI methylation level was an independent prognostic factor. Moreover, restoring TIPE3 expression significantly inhibited NPC cell proliferation, migration and invasion in vitro, and suppressed tumor growth and lung metastatic colonization in vivo, while silencing TIPE3 acted in an opposite way. Conclusions TIPE3 downregulation correlates with its CGI hypermethylation in several solid cancers. TIPE3 acts as a tumor suppressor in NPC, providing a further insight into NPC progression and representing a potential prognostic biomarker for NPC. Electronic supplementary material The online version of this article (10.1186/s13046-018-0881-5) contains supplementary material, which is available to authorized users.
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- 2018
10. RAB37 Hypermethylation Regulates Metastasis and Resistance to Docetaxel-Based Induction Chemotherapy in Nasopharyngeal Carcinoma
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Xin-Ran Tang, Qingmei He, Xiao-Jing Yang, Xiao-Hong Hong, Xiao-Jing Du, Ying Qin Li, Yuan Lei, Jun Ma, Xin Wen, Ying Sun, Jian Zhang, Na Liu, Ya-Qin Wang, and Pan-Pan Zhang
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0301 basic medicine ,Regulation of gene expression ,Cancer Research ,MMP2 ,business.industry ,medicine.disease ,Metastasis ,03 medical and health sciences ,030104 developmental biology ,Oncology ,Downregulation and upregulation ,Nasopharyngeal carcinoma ,Docetaxel ,DNA methylation ,Cancer research ,medicine ,Epigenetics ,business ,medicine.drug - Abstract
Purpose: Epigenetic alterations play important roles in metastasis and drug resistance through gene regulation. However, the functional features and molecular mechanisms of epigenetic changes remain largely unclear in nasopharyngeal carcinoma (NPC) metastasis. Experimental Design: Gene regulatory network analysis was used to identify metastatic-specific dysregulated genes between normal and NPC tissues and the expression was validated in published Gene-Expression Omnibus data set. The regulatory and functional role of RAB37 downregulation was examined in NPC and was validated in vitro and in vivo, and downstream target of RAB37 was explored. The clinical value of RAB37 methylation was evaluated in NPC metastasis and chemosensitivity. Results: We identified RAB37 as a specific hypermethylated gene that is most commonly downregulated in NPC. Moreover, RAB37 downregulation was attributed to hypermethylation of its promoter and was significantly associated with metastasis- and docetaxel chemoresistance-related features in NPC. Ectopic RAB37 overexpression suppressed NPC cell metastasis and enhanced chemosensitivity to docetaxel. Mechanistically, RAB37 colocalized with TIMP2, regulated TIMP2 secretion, inhibited downstream MMP2 activity, and consequently altered NPC cell metastasis. Furthermore, RAB37 hypermethylation was correlated with poor clinical outcomes in patients with NPC. We developed a prognostic model based on RAB37 methylation and N stage that effectively predicted an increased risk of distant metastasis and a favorable response to docetaxel-containing induction chemotherapy (IC) in NPC patients. Conclusions: This study shows that RAB37 hypermethylation is involved in NPC metastasis and chemoresistance, and that our prognostic model can identify patients who are at a high risk of distant metastasis and might benefit from for docetaxel IC.
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- 2018
11. HOPX hypermethylation promotes metastasis via activating SNAIL transcription in nasopharyngeal carcinoma
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Na Liu, Qian Zhong, Tianpeng Zhang, Ying-Qin Li, Xiaozhong Chen, Jun Ma, Xin-Ran Tang, Qingmei He, Xianyue Ren, Bin Cheng, Xin Wen, Bin Li, Tiebang Kang, Mu Sheng Zeng, and Xiao-Jing Yang
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Transcriptional Activation ,0301 basic medicine ,Science ,Transplantation, Heterologous ,Mice, Nude ,General Physics and Astronomy ,Kaplan-Meier Estimate ,Snail ,Biology ,Article ,General Biochemistry, Genetics and Molecular Biology ,Metastasis ,Histones ,03 medical and health sciences ,0302 clinical medicine ,Cell Line, Tumor ,biology.animal ,otorhinolaryngologic diseases ,medicine ,Animals ,Humans ,Epigenetics ,Neoplasm Metastasis ,Promoter Regions, Genetic ,Transcription factor ,Homeodomain Proteins ,Regulation of gene expression ,Mice, Inbred BALB C ,Multidisciplinary ,Tumor Suppressor Proteins ,Acetylation ,Nasopharyngeal Neoplasms ,General Chemistry ,DNA Methylation ,medicine.disease ,Gene Expression Regulation, Neoplastic ,Transplantation ,stomatognathic diseases ,030104 developmental biology ,Nasopharyngeal carcinoma ,030220 oncology & carcinogenesis ,DNA methylation ,Cancer research ,Female ,Snail Family Transcription Factors - Abstract
Nasopharyngeal carcinoma (NPC) is characterized by a high rate of local invasion and early distant metastasis. Increasing evidence indicates that epigenetic abnormalities play important roles in NPC development. However, the epigenetic mechanisms underlying NPC metastasis remain unclear. Here we investigate aberrantly methylated transcription factors in NPC tissues, and we identify the HOP homeobox HOPX as the most significantly hypermethylated gene. Consistently, we find that HOXP expression is downregulated in NPC tissues and NPC cell lines. Restoring HOPX expression suppresses metastasis and enhances chemosensitivity of NPC cells. These effects are mediated by HOPX-mediated epigenetic silencing of SNAIL transcription through the enhancement of histone H3K9 deacetylation in the SNAIL promoter. Moreover, we find that patients with high methylation levels of HOPX exhibit poor clinical outcomes in both the training and validation cohorts. In summary, HOPX acts as a tumour suppressor via the epigenetic regulation of SNAIL transcription, which provides a novel prognostic biomarker for NPC metastasis and therapeutic target for NPC treatment., HOPX is a transcription factor epigenetically silenced in several cancers. Here the authors, by analysing methylation profiles, identify HOPX as a suppressor of metastasis in nasopharyngeal carcinoma: mechanistically HOPX inhibits SNAIL transcription through deacetylation-mediated silencing.
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- 2017
12. Correction to: YPEL3 suppresses epithelial–mesenchymal transition and metastasis of nasopharyngeal carcinoma cells through the Wnt/β-catenin signaling pathway.
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Zhang, Jian, Wen, Xin, Ren, Xian-Yue, Li, Ying-Qin, Tang, Xin-Ran, Wang, Ya-Qin, He, Qing-Mei, Yang, Xiao-Jing, Sun, Ying, Liu, Na, and Ma, Jun
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EPITHELIAL-mesenchymal transition ,NASOPHARYNX cancer ,CELLULAR signal transduction ,WESTERN immunoblotting ,METASTASIS - Abstract
3 Effects of YPEL3 silencing on NPC cell migration and invasion in vitro. a Representative western blotting analysis of YPEL3 silencing in CNE-2 and SUNE-1 cells. Correction to: YPEL3 suppresses epithelial-mesenchymal transition and metastasis of nasopharyngeal carcinoma cells through the Wnt/ -catenin signaling pathway Correction to: YPEL3 suppresses epithelial-mesenchymal transition and metastasis of nasopharyngeal carcinoma cells through the Wnt/ -catenin signaling pathway. [Extracted from the article]
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- 2021
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13. miR-16 targets fibroblast growth factor 2 to inhibit NPC cell proliferation and invasion via PI3K/AKT and MAPK signaling pathways
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Xiao-Jing Yang, Na Liu, Ya-Qin Wang, Qingmei He, Jiewei Chen, Xin-Ran Tang, Ying-Qin Li, Jun Ma, Xin Wen, Jian Zhang, and Xianyue Ren
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0301 basic medicine ,MAPK/ERK pathway ,Lung Neoplasms ,Carcinogenesis ,Fibroblast growth factor ,Mice ,Phosphatidylinositol 3-Kinases ,0302 clinical medicine ,miR-16 ,Mice, Inbred BALB C ,Nasopharyngeal Carcinoma ,Gene Expression Regulation, Neoplastic ,tumor growth ,Oncology ,030220 oncology & carcinogenesis ,Disease Progression ,Mitogen-Activated Protein Kinases ,Signal transduction ,Research Paper ,MAP Kinase Signaling System ,Nasopharyngeal neoplasm ,Mice, Nude ,03 medical and health sciences ,Cell Line, Tumor ,otorhinolaryngologic diseases ,medicine ,metastasis ,Animals ,Humans ,Neoplasm Invasiveness ,fibroblast growth factor 2 ,Protein kinase B ,PI3K/AKT/mTOR pathway ,Cell Proliferation ,Cell growth ,business.industry ,Carcinoma ,Nasopharyngeal Neoplasms ,Genetic Therapy ,medicine.disease ,Xenograft Model Antitumor Assays ,MicroRNAs ,stomatognathic diseases ,030104 developmental biology ,Nasopharyngeal carcinoma ,Immunology ,Cancer research ,Neoplasm Recurrence, Local ,business ,Proto-Oncogene Proteins c-akt - Abstract
Dysregulation of miRNAs has been shown to contribute to the carcinogenesis and progression of nasopharyngeal carcinoma (NPC). Our previous microarray data showed that miR-16 expression is significantly decreased in archived NPC tissues. Here, we confirmed that miR-16 was reduced in NPC cell lines and freshly-frozen samples. Ectopic expression of miR-16 suppressed NPC cell proliferation, migration, and invasion in vitro and inhibited tumor growth and metastatic colonization in the lung in vivo. Furthermore, fibroblast growth factor 2 (FGF2) was identified as a direct target of miR-16, and both phosphoinositide-3- kinase/AKT (PI3K/AKT) and mitogen-activated protein kinase (MAPK) signaling pathways were repressed after miR-16 overexpression. In addition, the restoration of FGF2 reversed the suppressive effects of miR-16. Together, these results indicated that miR-16 suppresses NPC carcinogenesis and progression by targeting FGF2, thereby representing a potential target for miRNA-based therapy for NPC in the future.
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- 2015
14. EZH2-DNMT1-mediated epigenetic silencing of miR-142-3p promotes metastasis through targeting ZEB2 in nasopharyngeal carcinoma
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Pan-Pan Zhang, Xiao-Jing Yang, Na Liu, Xin Wen, Jun Ma, Ya-Qin Wang, Qingmei He, Xiao-Hong Hong, Ying Sun, Ying-Qin Li, Yuan Lei, Jian Zhang, and Xin-Ran Tang
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0301 basic medicine ,DNA (Cytosine-5-)-Methyltransferase 1 ,Cell ,Biology ,Article ,Metastasis ,Epigenesis, Genetic ,03 medical and health sciences ,0302 clinical medicine ,medicine ,otorhinolaryngologic diseases ,Gene silencing ,Humans ,Enhancer of Zeste Homolog 2 Protein ,Epigenetics ,Gene Silencing ,Molecular Biology ,Cells, Cultured ,Oligonucleotide Array Sequence Analysis ,Zinc Finger E-box Binding Homeobox 2 ,Nasopharyngeal Carcinoma ,EZH2 ,Nasopharyngeal Neoplasms ,Cell Biology ,medicine.disease ,stomatognathic diseases ,MicroRNAs ,030104 developmental biology ,medicine.anatomical_structure ,Nasopharyngeal carcinoma ,030220 oncology & carcinogenesis ,DNA methylation ,DNMT1 ,Cancer research - Abstract
Human nasopharyngeal carcinoma (NPC) has the highest metastatic rate in head and neck. However, the mechanisms underlying NPC metastasis remain unclear. Here using propensity-score-matched miRNA microarray analysis, miR-142-3p is identified to be the most correlated with distant-metastasis-free survival and downregulated in paraffin-embedded NPC with distant metastasis, which is validated in both internal cohort and external GEO dataset from Canada. miR-142 locus hypermethylation was observed and found to be associated with miR-142-3p downregulation in metastatic NPC. Furthermore, miR-142-3p was epigenetically silenced by EZH2-recruited DNMT1 and suppressed NPC cell metastasis and EMT. Intersecting PCR array gene profiling with bioinformatic prediction, we identify ZEB2 as a direct and functional target of miR-142-3p in NPC. Reversal of miR-142-3p silencing efficiently suppresses NPC cell invasion and metastasis. Moreover, epigenetic miR-142 hypermethylation is correlated with unfavorable prognosis in both training and validation cohorts. This study identifies miR-142-3p as a key suppressive regulator in NPC metastasis and reveals a DNMT1-mediated epigenetic mechanism for miR-142-3p silencing, providing a potential prognostic marker and therapeutic target to combat NPC metastasis.
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- 2018
15. Low SFRP1 Expression Correlates with Poor Prognosis and Promotes Cell Invasion by Activating the Wnt/β-Catenin Signaling Pathway in NPC
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Xin-Ran Tang, Jun Ma, Qing Mei He, Guan Qun Zhou, Xiao-Jing Yang, Ying Qin Li, Na Liu, Xian Yue Ren, Wei Jiang, Ying Sun, Ya Fei Xu, and Xin Wen
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Adult ,Male ,Cancer Research ,Blotting, Western ,Nasopharyngeal neoplasm ,Kaplan-Meier Estimate ,Biology ,Transfection ,medicine.disease_cause ,Polymerase Chain Reaction ,Disease-Free Survival ,Metastasis ,Mice ,Cyclin D1 ,otorhinolaryngologic diseases ,medicine ,Animals ,Humans ,Neoplasm Invasiveness ,RNA, Small Interfering ,Wnt Signaling Pathway ,Proportional Hazards Models ,Regulation of gene expression ,Mice, Inbred BALB C ,Nasopharyngeal Carcinoma ,Cell growth ,Carcinoma ,Wnt signaling pathway ,Membrane Proteins ,Nasopharyngeal Neoplasms ,Middle Aged ,Prognosis ,medicine.disease ,Immunohistochemistry ,Gene Expression Regulation, Neoplastic ,stomatognathic diseases ,Oncology ,Nasopharyngeal carcinoma ,Immunology ,Cancer research ,Heterografts ,Intercellular Signaling Peptides and Proteins ,Female ,Carcinogenesis - Abstract
Distant metastasis remains the predominant mode of treatment failure in nasopharyngeal carcinoma (NPC). Unfortunately, the molecular events underlying NPC metastasis remain poorly understood. Secreted frizzled-related protein 1 (SFRP1) plays an important role in tumorigenesis and progression. However, little is known about the function and mechanism of SFRP1 in NPC. Immunohistochemistry was used to determine SFRP1 expression levels in patients with NPC. SFRP1 function was evaluated using MTT, colony formation, wound-healing, Transwell assays, and in vivo models. The methylation level of SFRP1 in NPC cells was examined using bisulfate pyrosequencing; the Wnt/β-catenin signaling pathway genes were studied using Western blotting. Compared with patients with high SFRP1 expression, patients with low SFRP1 expression had worse overall survival [HR, 2.32; 95% confidence interval (CI), 1.36–3.94; P = 0.002], disease-free survival (HR, 1.98; 95% CI, 1.23–3.18; P = 0.005), and distant metastasis-free survival (HR, 2.07; 95% CI, 1.19–3.59; P = 0.009). Multivariate Cox regression analysis indicated that SFRP1 was an independent prognostic factor. Furthermore, SFRP1 was significantly downregulated in NPC cell lines. SFRP1 overexpression suppressed NPC cell proliferation, migration, and invasion in vitro and lung colonization in vivo. SFRP1 expression was restored after treatment with a demethylation agent, and the SFRP1 promoter region was hypermethylated in NPC cells. β-Catenin, c-Myc, and cyclin D1 were downregulated after SFRP1 restoration, which suggested that SFRP1 suppressed growth and metastasis by inhibiting the Wnt/β-catenin signaling pathway in NPC. SFRP1 provides further insight into NPC progression and may provide novel therapeutic targets for NPC treatment. Cancer Prev Res; 8(10); 968–77. ©2015 AACR.
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- 2015
16. Integrative evaluation of primary and metastatic lesion spectrum to guide anti-PD-LI therapy of non-small cell lung cancer: results from two randomized studies.
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Si-Cong Ma, Xin-Ran Tang, Li-Li Long, Xue Bai, Jian-Guo Zhou, Zhi-Jiao Duan, Jian Wang, Qiang John Fu, Hong-Bo Zhu, Xue-Jun Guo, Yan-Pei Zhang, Ze-Qin Guo, De-Hua Wu, and Zhong-Yi Dong
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NON-small-cell lung carcinoma , *ATEZOLIZUMAB , *METASTASIS , *CASTRATION-resistant prostate cancer , *CELLULAR therapy - Abstract
Objectives: Clinical benefits of immune-checkpoint blockade (ICB) versus standard chemotherapy have been established in unselected non-small cell lung cancer (NSCLC). However, the response to ICB therapy among patients is heterogeneous in clinical practice. Materials and Methods: We retrospectively assessed the predicitive effect of the primary and metastatic lesion spectrum (baseline sum of the longest diameters [SLD], number of metastatic sites and specific organ metastases) on the efficacy of atezolizumab over docetaxel in OAK and POPLAR trial cohorts. A decision model, termed DSO (Diameter-Site-Organ), based on the spectrum was developed and validated for guiding ICB. Results: Higher SLD (>38 mm) and more metastatic sites (>2) were characterized with pronounced overall survival (OS) benefits from atezolizumab versus docetaxel. Specifically, adrenal gland and brain metastases were identified as favorable predictors of atezolizumab treatment. The DSO model was developed in the discovery cohort to integrate the directive effect of the primary and metastatic lesion spectrum. Remarkably, a general pattern of enhanced efficacy of atezolizumab versus docetaxel was observed along with the increase of the DSO score. For patients with DSO score > 0, atezolizumab yielded a significantly prolonged OS than docetaxel, whereas OS was generally similar between two treatments in patients with DSO score < 0. Equivalent findings were also seen in the internal and external validation cohorts. Conclusions: The response to anti-PD-LI therapy among patients varied with the primary and metastatic lesion spectrum. The DSO-based system might provide promising medication guidance for ICB treatment in NSCLC patients. [ABSTRACT FROM AUTHOR]
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- 2021
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17. Prognostic value of MET protein overexpression and gene amplification in locoregionally advanced nasopharyngeal carcinoma
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Xianyue Ren, Na Liu, Xin Wen, Jun Ma, Jingping Yun, Xiao-Jing Yang, Wen-Fei Li, Qingmei He, Ya Fei Xu, Xin-Ran Tang, Jing Zeng, Ying Sun, and Ying-Qin Li
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Oncology ,Male ,medicine.medical_specialty ,Biopsy ,Nasopharyngeal neoplasm ,locoregionally advanced nasopharyngeal carcinoma ,Metastasis ,Internal medicine ,Gene duplication ,medicine ,Humans ,In Situ Hybridization, Fluorescence ,Nasopharyngeal Carcinoma ,medicine.diagnostic_test ,business.industry ,Incidence (epidemiology) ,Carcinoma ,Gene Amplification ,Nasopharyngeal Neoplasms ,Middle Aged ,Proto-Oncogene Proteins c-met ,medicine.disease ,Prognosis ,Gene Expression Regulation, Neoplastic ,Nasopharyngeal carcinoma ,Immunohistochemistry ,Female ,business ,MET overexpression ,MET amplification ,Fluorescence in situ hybridization ,Research Paper - Abstract
This study assessed the incidence and prognostic value of MET protein overexpression and gene amplification in locoregionally advanced nasopharyngeal carcinoma (NPC). Specimens from 376 consecutive patients with locoregionally advanced NPC were subjected to immunohistochemistry to analyze MET protein expression and fluorescence in situ hybridization to assess MET amplification status. In total, 139/376 (37.0%) patients had MET protein overexpression; of whom, 7/139 (5.0%) had MET amplification. MET overexpression was significantly associated with locoregional failure (P = 0.009), distant metastasis (P = 0.006) and death (P < 0.001); MET amplification was significantly associated with death (P = 0.021). A positive correlation was observed between MET copy number status and MET protein expression (r = 0.629, P < 0.001). Multivariate analysis demonstrated MET overexpression was an independent prognostic factor for overall survival (OS; HR, 1.99; 95% CI, 1.38–2.87; P < 0.001) and disease-free survival (DFS; HR, 1.85; 95% CI, 1.33–2.57; P < 0.001), and MET amplification was independently associated with poorer OS (HR, 4.24; 95% CI, 1.78-10.08; P < 0.001) and DFS (HR, 5.44; 95% CI, 2.44-12.09; P < 0.001). In conclusion, MET protein overexpression and gene amplification are independent prognostic factors for OS and DFS in locoregionally advanced nasopharyngeal carcinoma, and may provide therapeutic biomarkers to identify patients in whom MET inhibitors may be beneficial.
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- 2015
18. MiR-145 inhibits metastasis by targeting fascin actin-bundling protein 1 in nasopharyngeal carcinoma
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Na Liu, Xiao-Jing Yang, Xian Yue Ren, Ya Fei Xu, Qing Mei He, Jun Ma, Xin Wen, Ying Qin Li, and Xin-Ran Tang
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Nasopharyngeal neoplasm ,lcsh:Medicine ,Metastasis ,Mice ,Cell Line, Tumor ,microRNA ,medicine ,otorhinolaryngologic diseases ,Gene silencing ,Animals ,Humans ,Gene Silencing ,Neoplasm Metastasis ,lcsh:Science ,Fascin ,Mice, Inbred BALB C ,Multidisciplinary ,biology ,Carcinoma ,Microfilament Proteins ,lcsh:R ,Cell migration ,Nasopharyngeal Neoplasms ,Transfection ,medicine.disease ,MicroRNAs ,stomatognathic diseases ,Nasopharyngeal carcinoma ,biology.protein ,Cancer research ,Female ,lcsh:Q ,Carrier Proteins ,Research Article - Abstract
Background Based on our recent microarray analysis, we found that miR-145 was obviously downregulated in nasopharyngeal carcinoma (NPC) tissues. However, little is known about its function and mechanism involving in NPC development and progression. Methods Quantitative RT-PCR was used to detect miR-145 expression in NPC cell lines and clinical samples. Wound healing, Transwell migration and invasion, three-dimension spheroid invasion assays, and lung metastasis model were performed to test the migratory, invasive, and metastatic ability of NPC cells. Luciferase reporter assay, quantitative RT-PCR, and Western blotting were used to verify the target of miR-145. Results MiR-145 was obviously decreased in NPC cell lines and clinical samples (P
- Published
- 2015
19. MicroRNA-101 inhibits invasion and angiogenesis through targeting ITGA3 and its systemic delivery inhibits lung metastasis in nasopharyngeal carcinoma
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Ya Qin Wang, Xin-Ran Tang, Na Liu, Xin Wen, Jun Ma, Qing Mei He, Ying Qin Li, Xiao-Jing Yang, Xian Yue Ren, and Jian Zhang
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0301 basic medicine ,Adult ,Male ,Cancer Research ,Pathology ,medicine.medical_specialty ,Lung Neoplasms ,Angiogenesis ,Integrin alpha3 ,Immunology ,Biology ,Metastasis ,Neovascularization ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,Mice ,0302 clinical medicine ,Cell Movement ,Cell Line, Tumor ,microRNA ,medicine ,Carcinoma ,otorhinolaryngologic diseases ,Animals ,Humans ,Neoplasm Invasiveness ,Aged ,Cell Proliferation ,Nasopharyngeal Carcinoma ,Neovascularization, Pathologic ,Cell migration ,Nasopharyngeal Neoplasms ,Cell Biology ,Middle Aged ,medicine.disease ,Xenograft Model Antitumor Assays ,Gene Expression Regulation, Neoplastic ,stomatognathic diseases ,MicroRNAs ,030104 developmental biology ,Nasopharyngeal carcinoma ,030220 oncology & carcinogenesis ,Cancer research ,Ectopic expression ,Original Article ,Female ,medicine.symptom - Abstract
Clinically, distant metastasis after primary treatment remains a key problem in nasopharyngeal carcinoma (NPC), and the treatment outcome of metastatic NPC remains disappointing, so there is a pressing need to identify novel therapeutic strategies. In accordance with our previous microarray data, we found that miR-101 was downregulated in NPC clinical specimens and cell lines. Ectopic expression of miR-101 significantly suppressed NPC cell migration, invasion and angiogenesis in vitro and inhibited angiogenesis and metastasis in vivo using the chicken chorioallantoic membrane model. Furthermore, ITGA3 was identified and validated as a novel target of miR-101, and the restoration of ITGA3 expression potently rescued the suppressive effects of miR-101. In addition, NPC patients with high ITGA3 expression had poorer overall survival and distant metastasis-free survival than patients with low ITGA3 expression, and ITGA3 overexpression was an independent poor prognostic factor in NPC. More importantly, we demonstrated that the systemic delivery of lentivirus-mediated miR-101 abrogated the lung metastatic colonization formation of NPC cells without obvious toxicity. Our study elucidates the molecular mechanisms of miR-101/ITGA3 pathway in regulating NPC metastasis and angiogenesis, and the systemic delivery of miR-101 provides a potent evidence for the development of a novel microRNA-targeting anticancer strategy for NPC patients.
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- 2017
20. Microarray Expression Profiling of Long Non-Coding RNAs Involved in Nasopharyngeal Carcinoma Metastasis
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Xin-Ran Tang, Xin Wen, Ying-Qin Li, Ya-Qin Wang, Xianyue Ren, Na Liu, Jun Ma, Xiao-Jing Yang, Jian Zhang, and Qingmei He
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0301 basic medicine ,Microarray ,Carcinogenesis ,medicine.disease_cause ,Bioinformatics ,Metastasis ,lcsh:Chemistry ,0302 clinical medicine ,Cell Movement ,lcsh:QH301-705.5 ,Spectroscopy ,Oligonucleotide Array Sequence Analysis ,long non-coding RNA ,General Medicine ,Long non-coding RNA ,Computer Science Applications ,Gene Expression Regulation, Neoplastic ,Lymphatic Metastasis ,030220 oncology & carcinogenesis ,RNA, Long Noncoding ,microarray ,Biology ,Article ,Catalysis ,Inorganic Chemistry ,03 medical and health sciences ,Downregulation and upregulation ,Cell Line, Tumor ,otorhinolaryngologic diseases ,medicine ,Humans ,metastasis ,RNA, Messenger ,Physical and Theoretical Chemistry ,nasopharyngeal carcinoma ,Molecular Biology ,Microarray analysis techniques ,Gene Expression Profiling ,Carcinoma ,Organic Chemistry ,Computational Biology ,Nasopharyngeal Neoplasms ,Microarray Analysis ,medicine.disease ,Gene expression profiling ,stomatognathic diseases ,030104 developmental biology ,lcsh:Biology (General) ,lcsh:QD1-999 ,Nasopharyngeal carcinoma ,Case-Control Studies ,Cancer research ,Oligoribonucleotides, Antisense - Abstract
Increasing evidence has demonstrated a significant role for long non-coding RNAs (lncRNAs) in tumorigenesis. However, their functions in nasopharyngeal carcinoma (NPC) metastasis remain largely unknown. In this study, a model comparing high and low metastatic NPC cell lines (5-8F vs. 6-10B and S18 vs. S26) was constructed to determine the expression profile of lncRNAs using the microarray analysis, and we found 167 lncRNAs and 209 mRNAs were differentially expressed. Bioinformatic analysis indicated that the dysregulated mRNAs participated in important biological regulatory functions in NPC. Validation of 26 significantly dysregulated lncRNAs by qRT-PCR showed the expression patterns of 22 lncRNAs were in accordance with the microarray data. Furthermore, the expression level of ENST00000470135, which was the most upregulated lncRNA in high metastatic cell lines, was significantly higher in NPC cell lines and tissues with lymph node metastasis (LNM) and knocking down ENST00000470135 suppressed the migration, invasion and proliferation of NPC cells in vitro. In conclusion, our study revealed expression patterns of lncRNAs in NPC metastasis. The dysregulated lncRNAs may act as novel biomarkers and therapeutic targets for NPC.
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- 2016
21. Development and validation of a gene expression-based signature to predict distant metastasis in locoregionally advanced nasopharyngeal carcinoma: a retrospective, multicentre, cohort study.
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Tang, Xin-Ran, Li, Ying-Qin, Liang, Shao-Bo, Jiang, Wei, Liu, Fang, Ge, Wen-Xiu, Tang, Ling-Long, Mao, Yan-Ping, He, Qing-Mei, Yang, Xiao-Jing, Zhang, Yuan, Wen, Xin, Zhang, Jian, Wang, Ya-Qin, Zhang, Pan-Pan, Sun, Ying, Yun, Jing-Ping, Zeng, Jing, Li, Li, and Liu, Li-Zhi
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GENE expression , *METASTASIS , *CARCINOMA , *COHORT analysis , *CANCER chemotherapy - Abstract
Background: Gene expression patterns can be used as prognostic biomarkers in various types of cancers. We aimed to identify a gene expression pattern for individual distant metastatic risk assessment in patients with locoregionally advanced nasopharyngeal carcinoma.Methods: In this multicentre, retrospective, cohort analysis, we included 937 patients with locoregionally advanced nasopharyngeal carcinoma from three Chinese hospitals: the Sun Yat-sen University Cancer Center (Guangzhou, China), the Affiliated Hospital of Guilin Medical University (Guilin, China), and the First People's Hospital of Foshan (Foshan, China). Using microarray analysis, we profiled mRNA gene expression between 24 paired locoregionally advanced nasopharyngeal carcinoma tumours from patients at Sun Yat-sen University Cancer Center with or without distant metastasis after radical treatment. Differentially expressed genes were examined using digital expression profiling in a training cohort (Guangzhou training cohort; n=410) to build a gene classifier using a penalised regression model. We validated the prognostic accuracy of this gene classifier in an internal validation cohort (Guangzhou internal validation cohort, n=204) and two external independent cohorts (Guilin cohort, n=165; Foshan cohort, n=158). The primary endpoint was distant metastasis-free survival. Secondary endpoints were disease-free survival and overall survival.Findings: We identified 137 differentially expressed genes between metastatic and non-metastatic locoregionally advanced nasopharyngeal carcinoma tissues. A distant metastasis gene signature for locoregionally advanced nasopharyngeal carcinoma (DMGN) that consisted of 13 genes was generated to classify patients into high-risk and low-risk groups in the training cohort. Patients with high-risk scores in the training cohort had shorter distant metastasis-free survival (hazard ratio [HR] 4·93, 95% CI 2·99-8·16; p<0·0001), disease-free survival (HR 3·51, 2·43-5·07; p<0·0001), and overall survival (HR 3·22, 2·18-4·76; p<0·0001) than patients with low-risk scores. The prognostic accuracy of DMGN was validated in the internal and external cohorts. Furthermore, among patients with low-risk scores in the combined training and internal cohorts, concurrent chemotherapy improved distant metastasis-free survival compared with those patients who did not receive concurrent chemotherapy (HR 0·40, 95% CI 0·19-0·83; p=0·011), whereas patients with high-risk scores did not benefit from concurrent chemotherapy (HR 1·03, 0·71-1·50; p=0·876). This was also validated in the two external cohorts combined. We developed a nomogram based on the DMGN and other variables that predicted an individual's risk of distant metastasis, which was strengthened by adding Epstein-Barr virus DNA status.Interpretation: The DMGN is a reliable prognostic tool for distant metastasis in patients with locoregionally advanced nasopharyngeal carcinoma and might be able to predict which patients benefit from concurrent chemotherapy. It has the potential to guide treatment decisions for patients at different risk of distant metastasis.Funding: The National Natural Science Foundation of China, the National Science & Technology Pillar Program during the Twelfth Five-year Plan Period, the Natural Science Foundation of Guang Dong Province, the National Key Research and Development Program of China, the Innovation Team Development Plan of the Ministry of Education, the Health & Medical Collaborative Innovation Project of Guangzhou City, China, and the Program of Introducing Talents of Discipline to Universities. [ABSTRACT FROM AUTHOR]- Published
- 2018
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22. The feasibility of contralateral lower neck sparing intensity modulation radiated therapy for nasopharyngeal carcinoma patients with unilateral cervical lymph node involvement.
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Tang, Ling-Long, Tang, Xin-ran, Li, Wen-fei, Chen, Lei, Tian, Li, Lin, Ai-Hua, Sun, Ying, and Ma, Jun
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NASOPHARYNX cancer , *NASOPHARYNX cancer patients , *INTENSITY modulation (Optics) , *MAGNETIC resonance imaging , *HEAD & neck cancer , *MULTIVARIATE analysis , *CANCER treatment , *METASTASIS , *NECK , *RADIOTHERAPY , *DISEASE relapse , *PILOT projects , *TREATMENT effectiveness ,NASOPHARYNX tumors - Abstract
Objectives: To investigate the feasibility of contralateral lower neck sparing intensity modulation radiated therapy (IMRT) for nasopharyngeal carcinoma patients (NPC) with unilateral cervical lymph node metastasis.Materials and Methods: Retrospective review of 546 patients with unilateral cervical lymph node metastasis treated between November 2009 and February 2012 at one institution. All patients were staged using magnetic resonance imaging and received radical IMRT. Patients were classified into two groups: the inferior border of the negative neck irradiation field only covered Levels III to Va in Group 1; the inferior border covered entire neck down to Levels IV to Vb in Group 2.Results: Median follow-up was 49.9months (range, 1.3-69.2months). Four-year overall survival (OS:89.3% vs. 88.9%, P=0.91), disease-free survival (DFS:81.7% vs. 81.0%, P=0.91), distant metastasis-free survival (DMFS:88.2% vs. 87.9%, P=0.95), local relapse-free survival (LRFS:96.7% vs. 94.7%, P=0.70) and nodal relapse-free survival (NRFS: 96.1% vs. 95.9%, P=0.94) were not significantly different between Group 1 and Group 2. Twenty-two patients developed cervical lymph node relapse; of whom 20/22 (91.0%) developed unilateral relapse within pretreatment positive neck. Only one patient developed out-of-field relapse, though this patient also relapsed within the neck irradiation field (Level II). No clinicopathological feature tested had significant prognostic value for NRFS in multivariate analysis.Conclusions: In the IMRT and MRI era, contralateral lower neck sparing IMRT seems to be feasible for NPC patients with unilateral cervical lymph node metastasis. [ABSTRACT FROM AUTHOR]- Published
- 2017
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23. YPEL3 suppresses epithelial-mesenchymal transition and metastasis of nasopharyngeal carcinoma cells through the Wnt/β-catenin signaling pathway.
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Jian Zhang, Xin Wen, Xian-Yue Ren, Ying-Qin Li, Xin-Ran Tang, Ya-Qin Wang, Qing-Mei He, Xiao-Jing Yang, Ying Sun, Na Liu, and Jun Ma
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EPITHELIAL cells ,MESENCHYMAL stem cells ,METASTASIS ,CANCER cells ,NASOPHARYNX cancer ,CANCER treatment - Abstract
Background: Metastasis remains the major cause of death in nasopharyngeal carcinoma (NPC). Yippee-like 3 (YPEL3) plays an important role in tumorigenesis. However, its function and mechanism in NPC has not been systematically explored. Methods: We evaluated YPEL3 expression in NPC cell lines and tissues using real-time PCR and western blotting. Then, we established NPC cell lines that stably overexpressed YPEL3 and knocked down YPEL3 expression to explore its function in NPC in vitro and in vivo. Additionally, we investigated the potential mechanism of YPEL3 action by identifying the Wnt/β-catenin signaling pathway downstream genes using western blotting. Results: YPEL3 was downregulated in NPC cell lines and tissue samples. Ectopic expression of YPEL3 inhibited NPC cell migration and invasion in vitro; while silencing of YPEL3 promoted NPC cell migration and invasion. Further study indicated that overexpression of YPEL3 inhibited NPC cell epithelial-mesenchymal transition (EMT) and that silencing it enhanced EMT. Overexpression of YPEL3 suppressed NPC cell lung metastasis in vivo. The mechanism study determined that YPEL3 suppressed the expression levels of Wnt/β-catenin signaling pathway downstream genes and the nuclear translocation of β-catenin. Conclusions: YPEL3 suppresses NPC EMT and metastasis by suppressing the Wnt/β-catenin signaling pathway, which would help better understanding the molecular mechanisms of NPC metastasis and provide novel therapeutic targets for NPC treatment. [ABSTRACT FROM AUTHOR]
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- 2016
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24. High expression of Talin-1 is associated with poor prognosis in patients with nasopharyngeal carcinoma.
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Ya-Fei Xu, Xian-Yue Ren, Ying-Qin Li, Qing-Mei He, Xin-Ran Tang, Ying Sun, Jian-Yong Shao, Wei-Hua Jia, Tie-Bang Kang, Mu-Sheng Zeng, Na Liu, and Jun Ma
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NASOPHARYNX cancer patients ,TALINS (Proteins) ,CYTOSKELETAL proteins ,METASTASIS ,GENE expression ,REVERSE transcriptase polymerase chain reaction - Abstract
Background: Talin-1 is a cytoskeletal protein that plays an important role in tumourgenesis, migration and metastasis in several malignant tumors. The aim of this study was to evaluate the expression and prognostic value of Talin-1 in nasopharyngeal carcinoma (NPC). Methods: Talin-1 mRNA and protein expression were examined in NPC cell lines and clinical nasopharyngeal tissues by quantitative RT-PCR, agarose gel electrophoresis and western blotting. The expression of Talin-1 was analyzed by immunohistochemical staining in 233 paraffin-embedded NPC specimens with clinical follow-up data and cox regression analysis was used to identify independent prognostic factors. The functional role of Talin-1 in NPC cell lines was evaluated by small interfering RNA-mediated depletion of the protein followed by the wound healing and transwell invasion assays. Results: The expression of Talin-1 was significantly upregulated in most NPC cell lines and clinical tissues at both the mRNA and protein levels. High expression of Talin-1 was significantly associated with distant metastasis (P= 0.001) and patient death (P= 0.001). In addition, high expression of Talin-1 was associated with significantly poorer overall survival (OS: HR, 2.15; 95% CI, 1.28-3.63; P= 0.003) and poorer distant metastasis-free survival (DMFS: HR, 2.39; 95% CI, 1.38-4.15; P= 0.001). Cox regression analysis indicated that high expression of Talin-1 and TNM stage were independent prognostic indicators (both P < 0.05). Stratified analysis demonstrated that high expression of Talin-1 was associated with significantly poorer survival in patients with advanced stage disease (stage III-IV, HR, 1.91; 95% CI, 1.09-3.35; P = 0.02 for OS and HR, 2.22; 95% CI, 1.24-3.99; P = 0.006 for DMFS). Furthermore, the depletion of Talin-1 suppressed the migratory and invasive ability of NPC cells in vitro. Conclusions: Our data demonstrate that high expression of Talin-1 is associated with significantly poorer OS and poorer DMFS in NPC and depletion of Talin-1 expression inhibited NPC cell migration and invasion. Talin-1 may serve as novel prognostic biomarker in NPC. [ABSTRACT FROM AUTHOR]
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- 2015
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25. MiR-145 Inhibits Metastasis by Targeting Fascin Actin-Bundling Protein 1 in Nasopharyngeal Carcinoma.
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Li, Ying-Qin, He, Qing-Mei, Ren, Xian-Yue, Tang, Xin-Ran, Xu, Ya-Fei, Wen, Xin, Yang, Xiao-Jing, Ma, Jun, and Liu, Na
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MICRORNA ,MICROFILAMENT proteins ,METASTASIS ,NASOPHARYNX cancer ,GENE targeting ,DNA microarrays - Abstract
Background: Based on our recent microarray analysis, we found that miR-145 was obviously downregulated in nasopharyngeal carcinoma (NPC) tissues. However, little is known about its function and mechanism involving in NPC development and progression. Methods: Quantitative RT-PCR was used to detect miR-145 expression in NPC cell lines and clinical samples. Wound healing, Transwell migration and invasion, three-dimension spheroid invasion assays, and lung metastasis model were performed to test the migratory, invasive, and metastatic ability of NPC cells. Luciferase reporter assay, quantitative RT-PCR, and Western blotting were used to verify the target of miR-145. Results: MiR-145 was obviously decreased in NPC cell lines and clinical samples (P<0.01). Ectopic overexpression of miR-145 significantly inhibited the migratory and invasive ability of SUNE-1 and CNE-2 cells. In addition, stably overexpressing of miR-145 in SUNE-1 cells could remarkably restrain the formation of metastatic nodes in the lungs of mice. Furthermore, fascin actin-bundling protein 1 (FSCN1) was verified as a target of miR-145, and silencing FSCN1 with small RNA interfering RNA could suppress NPC cell migration and invasion. Conclusions: Our findings demonstrated that miR-145 function as a tumor suppressor in NPC development and progression via targeting FSCN1, which could sever as a potential novel therapeutic target for patients with NPC. [ABSTRACT FROM AUTHOR]
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- 2015
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26. Correction to: YPEL3 suppresses epithelial–mesenchymal transition and metastasis of nasopharyngeal carcinoma cells through the Wnt/β-catenin signaling pathway.
- Author
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Zhang, Jian, Wen, Xin, Ren, Xian-Yue, Li, Ying-Qin, Tang, Xin-Ran, Wang, Ya-Qin, He, Qing-Mei, Yang, Xiao-Jing, Sun, Ying, Liu, Na, and Ma, Jun
- Subjects
EPITHELIAL-mesenchymal transition ,METASTASIS ,CARCINOMA ,CELLS - Abstract
An amendment to this paper has been published and can be accessed via the original article. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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27. High expression of Talin-1 is associated with poor prognosis in patients with nasopharyngeal carcinoma
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Jian Yong Shao, Ya Fei Xu, Mu Sheng Zeng, Wei Hua Jia, Na Liu, Tie Bang Kang, Ying Qin Li, Ying Sun, Jun Ma, Qing Mei He, Xin-Ran Tang, and Xian Yue Ren
- Subjects
Oncology ,Male ,Talin ,medicine.medical_specialty ,Cancer Research ,Nasopharyngeal neoplasm ,macromolecular substances ,Disease-Free Survival ,Metastasis ,Surgical oncology ,Cell Movement ,Internal medicine ,Cell Line, Tumor ,Carcinoma ,medicine ,Biomarkers, Tumor ,Genetics ,Humans ,Neoplasm Invasiveness ,Talin-1 ,RNA, Messenger ,Aged ,Neoplasm Staging ,Regulation of gene expression ,Nasopharyngeal Carcinoma ,business.industry ,Nasopharyngeal Neoplasms ,Biomarker ,Middle Aged ,medicine.disease ,Prognosis ,Gene Expression Regulation, Neoplastic ,Nasopharyngeal carcinoma ,Immunohistochemistry ,Biomarker (medicine) ,Female ,business ,Research Article - Abstract
Background Talin-1 is a cytoskeletal protein that plays an important role in tumourgenesis, migration and metastasis in several malignant tumors. The aim of this study was to evaluate the expression and prognostic value of Talin-1 in nasopharyngeal carcinoma (NPC). Methods Talin-1 mRNA and protein expression were examined in NPC cell lines and clinical nasopharyngeal tissues by quantitative RT-PCR, agarose gel electrophoresis and western blotting. The expression of Talin-1 was analyzed by immunohistochemical staining in 233 paraffin-embedded NPC specimens with clinical follow-up data and cox regression analysis was used to identify independent prognostic factors. The functional role of Talin-1 in NPC cell lines was evaluated by small interfering RNA-mediated depletion of the protein followed by the wound healing and transwell invasion assays. Results The expression of Talin-1 was significantly upregulated in most NPC cell lines and clinical tissues at both the mRNA and protein levels. High expression of Talin-1 was significantly associated with distant metastasis (P = 0.001) and patient death (P = 0.001). In addition, high expression of Talin-1 was associated with significantly poorer overall survival (OS: HR, 2.15; 95% CI, 1.28-3.63; P = 0.003) and poorer distant metastasis-free survival (DMFS: HR, 2.39; 95% CI, 1.38-4.15; P = 0.001). Cox regression analysis indicated that high expression of Talin-1 and TNM stage were independent prognostic indicators (both P
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28. YPEL3 suppresses epithelial–mesenchymal transition and metastasis of nasopharyngeal carcinoma cells through the Wnt/β-catenin signaling pathway
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Jian Zhang, Ying Sun, Ya Qin Wang, Xian Yue Ren, Xin-Ran Tang, Ying Qin Li, Jun Ma, Qing Mei He, Xin Wen, Xiao-Jing Yang, and Na Liu
- Subjects
0301 basic medicine ,Cancer Research ,Pathology ,medicine.medical_specialty ,Cell ,Metastasis ,03 medical and health sciences ,0302 clinical medicine ,Nasopharyngeal carcinoma ,medicine ,otorhinolaryngologic diseases ,Gene silencing ,Epithelial–mesenchymal transition ,Wnt/β-catenin ,Chemistry ,Research ,Wnt signaling pathway ,Cell migration ,medicine.disease ,stomatognathic diseases ,030104 developmental biology ,medicine.anatomical_structure ,Oncology ,YPEL3 ,030220 oncology & carcinogenesis ,Cancer research ,Ectopic expression ,Signal transduction - Abstract
Background Metastasis remains the major cause of death in nasopharyngeal carcinoma (NPC). Yippee-like 3 (YPEL3) plays an important role in tumorigenesis. However, its function and mechanism in NPC has not been systematically explored. Methods We evaluated YPEL3 expression in NPC cell lines and tissues using real-time PCR and western blotting. Then, we established NPC cell lines that stably overexpressed YPEL3 and knocked down YPEL3 expression to explore its function in NPC in vitro and in vivo. Additionally, we investigated the potential mechanism of YPEL3 action by identifying the Wnt/β-catenin signaling pathway downstream genes using western blotting. Results YPEL3 was downregulated in NPC cell lines and tissue samples. Ectopic expression of YPEL3 inhibited NPC cell migration and invasion in vitro; while silencing of YPEL3 promoted NPC cell migration and invasion. Further study indicated that overexpression of YPEL3 inhibited NPC cell epithelial–mesenchymal transition (EMT) and that silencing it enhanced EMT. Overexpression of YPEL3 suppressed NPC cell lung metastasis in vivo. The mechanism study determined that YPEL3 suppressed the expression levels of Wnt/β-catenin signaling pathway downstream genes and the nuclear translocation of β-catenin. Conclusions YPEL3 suppresses NPC EMT and metastasis by suppressing the Wnt/β-catenin signaling pathway, which would help better understanding the molecular mechanisms of NPC metastasis and provide novel therapeutic targets for NPC treatment.
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29. TIPE3 hypermethylation correlates with worse prognosis and promotes tumor progression in nasopharyngeal carcinoma.
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Wen, Xin, Li, Ying-Qing, Zhang, Jian, He, Qing-Mei, Yang, Xiao-Jing, Tang, Xin-Ran, Wang, Ya-Qin, Zhang, Pan-Pan, Ma, Jun, Liu, Na, Ren, Xian-Yue, Cheng, Bin, and Chen, Xiao-Zhong
- Subjects
DNA methylation ,NASOPHARYNX cancer ,TUMOR necrosis factors ,BIOLOGICAL tags ,MESSENGER RNA - Abstract
Background: Increasing evidence recognizes that DNA methylation abnormalities play critical roles in cancer development. Our previous genome-wide methylation profile showed that tumor necrosis factor-alpha-induced protein 8 like 3 (TIPE3) was hypermethylated in nasopharyngeal carcinoma (NPC). However, the relationship between TIPE3 methylation and its mRNA expression, as well as its biological roles in NPC are unknown. Methods: Bisulfite pyrosequencing and quantitative RT-PCR were performed to quantify the TIPE3 methylation and expression levels. Kaplan-Meier curves and Cox regression analysis were used to estimate the correlation between TIPE3 methylation levels and survival in two patient cohorts collected from two hospitals (n = 441). The MTT, colony formation, Transwell migration and invasion assays, and xenograft tumor growth and lung metastatic colonization models were used to identify the functions of TIPE3 on NPC cells. Results: We found that TIPE3 CpG island (CGI) was hypermethylated and its mRNA levels were downregulated in many cancers, including NPC. TIPE3 downregulation was associated with its CGI hypermethylation. Furthermore, NPC patients with high TIPE3 CGI methylation levels had poorer clinical outcomes than those with low methylation levels. The TIPE3 CGI methylation level was an independent prognostic factor. Moreover, restoring TIPE3 expression significantly inhibited NPC cell proliferation, migration and invasion in vitro, and suppressed tumor growth and lung metastatic colonization in vivo, while silencing TIPE3 acted in an opposite way. Conclusions: TIPE3 downregulation correlates with its CGI hypermethylation in several solid cancers. TIPE3 acts as a tumor suppressor in NPC, providing a further insight into NPC progression and representing a potential prognostic biomarker for NPC. [ABSTRACT FROM AUTHOR]
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- 2018
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30. Corrigendum to "NFAT1 hypermethylation promotes epithelial‐mesenchymal transition and metastasis in nasopharyngeal carcinoma by activating ITGA6 transcription" [Neoplasia 21 (2019): 311–321].
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Zhang, Jian, Zheng, Zi-Qi, Yuan, Ya-Wei, Zhang, Pan-Pan, Li, Ying-Qin, Wang, Ya-Qin, Tang, Xin-Ran, Wen, Xin, Hong, Xiao-Hong, Lei, Yuan, He, Qing-Mei, Yang, Xiao-Jing, Sun, Ying, Ma, Jun, and Liu, Na
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EPITHELIAL-mesenchymal transition , *NASOPHARYNX cancer , *TUMORS , *METASTASIS , *TRANSGENIC organisms - Published
- 2021
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31. NFAT1 Hypermethylation Promotes Epithelial-Mesenchymal Transition and Metastasis in Nasopharyngeal Carcinoma by Activating ITGA6 Transcription.
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Zhang, Jian, Zheng, Zi-Qi, Yuan, Ya-Wei, Zhang, Pan-Pan, Li, Ying-Qin, Wang, Ya-Qin, Tang, Xin-Ran, Wen, Xin, Hong, Xiao-Hong, Lei, Yuan, He, Qing-Mei, Yang, Xiao-Jing, Sun, Ying, Ma, Jun, and Liu, Na
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METASTASIS , *CARCINOMA - Abstract
Abstract DNA methylation is an important epigenetic change in carcinogenesis. However, the function and mechanism of DNA methylation dysregulation in nasopharyngeal carcinoma (NPC) is still largely unclear. Our previous genome-wide microarray data showed that NFAT1 is one of the most hypermethylated transcription factor genes in NPC tissues. Here, we found that NFAT1 hypermethylation contributes to its down-regulation in NPC. NFAT1 overexpression inhibited cell migration, invasion, and epithelial-mesenchymal transition in vitro and tumor metastasis in vivo. We further established that the tumor suppressor effect of NFAT1 is mediated by its inactivation of ITGA6 transcription. Our findings suggest the significance of activating NFAT1 / ITGA6 signaling in aggressive NPC, defining a novel critical signaling mechanism that drives NPC invasion and metastasis and providing a novel target for future personalized therapy. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
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