共查询到20条相似文献,搜索用时 15 毫秒
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Cheng Lin Keyu Lin Bin Zhang Ying Su Qiaojuan Guo Tianzhu Lu Yuanji Xu Shaojun Lin Jingfeng Zong Jianji Pan 《The oncologist》2022,27(4):e340
BackgroundNasopharyngeal carcinoma is an Epstein-Barr virus (EBV)-associated tumor that is highly common in southern China. Our previous sequencing data demonstrated that the EBV-encoded microRNA BART8-3p was most upregulated in nasopharyngeal carcinoma (NPC) and was closely associated with the metastasis of NPC. However, the values of plasma BART8-3p in NPC patients have not yet been well characterized.Material and MethodsWe quantified plasma BART8-3p expression by quantitative real-time PCR in 205 newly diagnosed NPC patients. Kaplan-Meier analysis was used to compare overall survival (OS), distant metastasis-free survival (DMFS), and locoregional relapse-free survival (LRRFS) between the groups.ResultsPlasma pretreatment BART8-3p was highly expressed in NPC patients compared with healthy controls. Pretreatment BART8-3p yielded a 92% predictive value for detecting NPC. Importantly, BART8-3p decreased dramatically after therapy relative to pretreatment levels. High levels of pretreatment or post-treatment BART8-3p were associated with worse OS, DMFS, and LRRFS. Multivariate analysis showed that high pretreatment or post-treatment BART8-3p was an independent unfavorable prognostic marker for OS (HR 3.82, 95% CI 1.77-8.24, P = .001 or HR 2.74, 95% CI 1.27-5.91, P = .010), DMFS (HR 2.82, 95% CI 1.36-5.85, P = .005 or HR 3.27, 95% CI 1.57-6.81, P = .002), and LRRFS (HR 1.94, 95% CI 1.12-3.35, P = .018 or HR 2.03, 95% CI 1.14-3.62, P = .016) in NPC. Subgroup analysis revealed that for patients with locally advanced NPC with high levels of pretreatment BART8-3p (n = 58), more cycles of chemotherapy (≥6 cycles) tended to prolong OS (P = .070). Over 50% (6/11) patients with high levels of post-treatment BART8-3p presented distant metastasis.ConclusionPlasma BART8-3p is a promising biomarker for the detection and prognosis of NPC. 相似文献
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Octavia Ramayanti Sandra A.W.M. Verkuijlen Putri Novianti Chantal Scheepbouwer Branislav Misovic Danijela Koppers-Lalic Jan van Weering Lisa Beckers Marlinda Adham Debora Martorelli Jaap M. Middeldorp Dirk Michiel Pegtel 《International journal of cancer. Journal international du cancer》2019,144(10):2555-2566
Cell-free microRNA (miRNA) in biofluids released by tumors in either protein or vesicle-bound form, represent promising minimally-invasive cancer biomarkers. However, a highly abundant non-tumor background in human plasma and serum complicates the discovery and detection of tumor-selective circulating miRNAs. We performed small RNA sequencing on serum and plasma RNA from Nasopharyngeal Carcinoma (NPC) patients. Collectively, Epstein Barr virus-encoded miRNAs, more so than endogenous miRNAs, signify presence of NPC. However, RNAseq-based EBV miRNA profiles differ between NPC patients, suggesting inter-tumor heterogeneity or divergent secretory characteristics. We determined with sensitive qRT-PCR assays that EBV miRNAs BART7-3p, BART9-3p and BART13-3p are actively secreted by C666.1 NPC cells bound to extracellular vesicles (EVs) and soluble ribonucleoprotein complexes. Importantly, these miRNAs are expressed in all primary NPC tumor biopsies and readily detected in nasopharyngeal brushings from both early and late-stage NPC patients. Increased levels of BART7-3p, BART9-3p and particularly BART13-3p, distinguish NPC patient sera from healthy controls. Receiver operating characteristic curve analysis using sera from endemic NPC patients, other head and neck cancers and individuals with asymptomatic EBV-infections reveals a superior diagnostic performance of EBV miRNAs over anti-EBNA1 IgA serology and EBV-DNA load (AUC 0.87–0.96 vs 0.86 and 0.66 respectively). The high specificity of circulating EBV-BART13-3p (97%) for NPC detection is in agreement with active secretion from NPC tumor cells. We conclude EV-bound BART13-3p in circulation is a promising, NPC-selective, biomarker that should be considered as part of a screening strategy to identify NPC in endemic regions. 相似文献
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Qijia Yan Zhaoyang Zeng Zhaojian Gong Wenling Zhang Xiayu Li Baoyu He Yali Song Qiao Li Yong Zeng Qianjin Liao Pan Chen Lei Shi Songqing Fan Bo Xiang Jian Ma Ming Zhou Xiaoling Li Jianbo Yang Wei Xiong Guiyuan Li 《Oncotarget》2015,6(39):41766-41782
Epstein-Barr virus (EBV) infection is closely associated with tumorigenesis and development of nasopharyngeal carcinoma (NPC), but the underlying molecular mechanisms remain poorly understood. It has been recently reported that EBV encodes 44 mature miRNAs, some of which were found to promote tumor development by targeting virus-infected host genes or self-viral genes. However, few targets of EBV encoded-miRNAs that are related to NPC development have been identified to date. In this study, we revealed that in NPC cells, EBV-miR-BART10-3p directly targets BTRC gene that encodes βTrCP (beta-transducin repeat containing E3 ubiquitin protein ligase). We found that EBV-miR-BART10-3p expression in clinical samples from a cohort of 106 NPC patients negatively correlated with BTRC expression levels. Over-expression of EBV-miR-BART10-3p and down-regulation of BTRC were associated with poor prognosis in NPC patients. EBV-miR-BART10-3p promoted the invasion and migration cabilities of NPC cells through the targeting of BTRC and regulation of the expression of the downstream substrates β-catenin and Snail. As a result, EBV-miR-BART10-3p facilitated epithelial-mesenchymal transition of NPC. Our study presents an unreported mechanism underlying EBV infection in NPC carcinogenesis, and provides a potential novel biomarker for NPC diagnosis, treatment and prognosis. 相似文献
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Modulation of LMP2A Expression by a Newly Identified Epstein-Barr Virus-Encoded MicroRNA miR-BART22
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Raymond Wai-Ming Lung Joanna Hung-Man Tong Ying-Man Sung Pak-Sing Leung David Chi-Heng Ng Shuk-Ling Chau Anthony Wing-Hung Chan Enders Kai-On Ng Kwok-Wai Lo Ka-Fai To 《Neoplasia (New York, N.Y.)》2009,11(11):1174-1184
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BART miRNA是EBV编码的miRNA前体经选择剪切的产物,能够通过影响病毒自身或宿主基因表达,发挥癌基因或抑癌基因作用,参与肿瘤细胞的增殖、生长、凋亡及转移的调控,或是影响肿瘤放化疗的效果,以及影响筛查和预后。miR-BARTs在所有潜伏类型的EBV中均有表达,但在NPC细胞系中表达最显著,表明miR-BARTs与NPC的发生发展有关。阐明miR-BART在NPC中的作用机制对于NPC的筛查、诊断以及治疗等方面的临床实践均具有指导意义。 相似文献
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Circulating Epstein–Barr virus microRNAs miR‐BART7 and miR‐BART13 as biomarkers for nasopharyngeal carcinoma diagnosis and treatment
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Shaojun Lin Rob J.A. Verhoeven Shuang Tong Yixin Chen Mingfang Ji Weimin Cheng Sai‐Wah Tsao Maria Lung Jianji Pan Honglin Chen 《International journal of cancer. Journal international du cancer》2015,136(5):E301-E312
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Xia T O'Hara A Araujo I Barreto J Carvalho E Sapucaia JB Ramos JC Luz E Pedroso C Manrique M Toomey NL Brites C Dittmer DP Harrington WJ 《Cancer research》2008,68(5):1436-1442
EBV-encoded microRNAs (miRNAs) have been identified and their functions are being studied. The expression pattern of these miRNAs in clinical samples of EBV-associated non-Hodgkin's lymphomas is unknown. We analyzed five primary "endemic" pediatric Burkitt's lymphomas (BL), two acquired immunodeficiency syndrome (AIDS)-related type I latency BL lines, a type III latency line, three EBV(+) primary effusion lymphomas (PEL), and three AIDS-related diffuse large B-cell lymphomas (DLBCL) for expression of EBV-encoded miRNAs. A markedly elevated expression of miRNA BHRF1-3 in type III relative to its parental type I BL line was found. Primary unmanipulated type I BLs and EBV(+) PELs expressed high levels of BART2 miRNA, whereas DLBCLs expressed both BART2 and BHRF1-3 species. BHRF1-3 miRNA expression inversely correlated with levels of a putative cellular target, the IFN-inducible T-cell attracting chemokine CXCL-11/I-TAC, and suppression of this factor was reversed by transfection of an antisense oligo to the EBV miRNA BHRF1-3. EBV-encoded miRNAs are expressed in primary lymphomas classically linked to the virus and are associated with the viral latency status. Targeted suppression of CXCL-11/I-TAC by a viral-encoded miRNA may serve as an immunomodulatory mechanism in these tumors. 相似文献
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Koshiol J Gulley ML Zhao Y Rubagotti M Marincola FM Rotunno M Tang W Bergen AW Bertazzi PA Roy D Pesatori AC Linnoila I Dittmer D Goldstein AM Caporaso NE McShane LM Wang E Landi MT 《British journal of cancer》2011,105(2):320-326
Background:
We conducted the first analysis of viral microRNAs (miRNAs) in lung cancer, with a focus on Epstein–Barr virus (EBV).Methods:
We evaluated viral miRs with a two-channel oligo-array targeting mature, anti-sense miRNAs in 290 cases. In 48 cases, we compared microarray and real-time quantitative PCR (qPCR) expression for three EBV miRNAs. We tested for EBV DNA, RNA, and protein in tumour tissue from six cases with and six cases without strong qPCR-based evidence of EBV miRNAs.Results:
The EBV miRNAs strongly differentiated between adenocarcinoma and squamous cell carcinoma using the microarray (P<0.01 for 9 out of 16 EBV miRNAs). However, microarray and qPCR measurements of BART1, BART2, and BHRF1–3 expression were not significantly correlated (P=0.53, 0.94, and 0.47, respectively). Although qPCR provided substantial evidence of EBV miRNAs in 7 out of 48 cases, only 1 of these 7 cases had detectable EBV DNA in tumour tissue. None had detectable EBV RNA or protein by histochemical stains.Conclusion:
In a comprehensive evaluation of EBV miRNA, DNA, RNA, and protein in lung cancer, we found little evidence of EBV in lung tumour tissue. Discrepancies between microarray- and qPCR-based strategies highlight the difficulty of validating molecular markers of disease. Our results do not support a role of EBV in lung cancer. 相似文献12.
目的 探讨EB病毒(epstein⁃barr virus,EBV)编码的EBV⁃miR⁃BART17⁃5p对鼻咽癌细胞增殖及迁移的调控及其机制。方法 将慢病毒Vector control和 EBV⁃miR⁃BART17⁃5p mimic分别感染至HK1⁃EBV细胞,记为Vector control组和Mimic组,采用RT⁃qPCR验证慢病毒感染效果;EdU和CCK⁃8实验分别检测细胞的增殖能力;平板克隆形成实验检测细胞的集落形成能力;细胞划痕实验及Transwell 细胞迁移实验检测细胞的迁移能力;Western blot检测EBV⁃miR⁃BART17⁃5p靶基因PTEN的蛋白表达水平。结果 与Vector control组比较,Mimic组HK1⁃EBV细胞中EBV⁃miR⁃BART17⁃5p表达量显著升高(P<0.001),细胞增殖、集落形成和迁移能力均明显增强(均P<0.05),PTEN蛋白表达水平显著降低(P<0.001)。结论 EBV⁃miR⁃BART17⁃5p能调控鼻咽癌细胞HK1⁃EBV增殖和迁移,其作用机制可能与EBV⁃miR⁃BART17⁃5p反向调控肿瘤抑制因子PTEN表达有关。 相似文献
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目的:探讨ebv-miRNA在低分化NPC细胞株C666-1(EBV+)和CNE-2Z(EBV表达水平随传代次数增加而逐渐降低)中的差异性表达进而分析其功能.方法:常规培养NPC细胞株C666-1和CNE-2Z,分别提取总RNA并进行质检;RT-PCR检测LMP-1和LMP-2A mRNA的表达以判断EBV的感染情况;miRNA芯片技术检测EBV miRNAs的表达并对其表达谱进行差异性分析;荧光定量RT-PCR进行验证;复习文献了解ebv-miRNA调控的靶基因以了解其功能.结果:从C666-1和CNE-2Z两株细胞抽提的总RNA纯度高,A260/A280〉2.0,A260/A230〉2.1,RNA完整性好.C666-1具有比CNE-2Z更高的LMP-1和LMP-2A mRNA表达.ebv-miRNA表达谱的差异分析表明39个ebv-miRNAs中19个在两株细胞显著差异性表达;荧光定量RT-PCR结果证实ebv-miR-BHRF1-1和ebv-miR-BART14*在C666-1中表达升高而ebv-miR-BART8*表达降低,与芯片结果趋势一致;复习文献,EBV miRNAs功能远不清楚,少数已知的靶基因涉及信号转导、转录调控、细胞凋亡、增殖、免疫反应和病毒DNA复制等方面.结论:ebv-miRNA在低分化NPC中具有差异性表达并广泛参与基因调控.不同NPC细胞中EBV miRNA表达差异预示着基于ebv-miRNA的NPC个性化治疗的可能性. 相似文献
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Cheng-Lung Hsu Yung-Chia Kuo Yenlin Huang Yin-Cheng Huang Kar-Wai Lui Kai-Ping Chang Tung-Liang Lin Hsien-Chi Fan An-Chi Lin Chia-Hsun Hsieh Li-Yu Lee Hung-Ming Wang Hsin-Pai Li Yu-Sun Chang 《Oncotarget》2015,6(31):31323-31334
Nasopharyngeal carcinoma (NPC) is an Epstein Barr virus (EBV)-related malignancy in which the tumor microenvironment plays a pivotal role in tumor progression. Here, we developed two patient-derived xenograft (PDX) mouse lines from engrafted NPC metastatic tumors. Positive staining for EBV-encoded small RNAs confirmed that these tumors harbored EBV, and gene expression profile analyses further showed that the PDX was highly similar to the primary parent tumor. In vivo drug screening using the PDX system demonstrated that gemcitabine had the best antitumor effect among the tested drugs. The donor of this PDX also showed excellent responsiveness to gemcitabine treatment. The combination of gemcitabine and valproic acid exerted synergistic antitumor effects. Further addition of ganciclovir to this two-drug combination regimen enhanced cytolytic viral activation, yielding the best antitumor response among tested regimens. Treatment with this three-drug combination regimen decreased plasma EBV-DNA load, tumor viral concentration, and the number of viable tumor cells to a greater extent than the two-drug gemcitabine and valproic acid combination. These results highlight the value of PDX models in the development of EBV-targeted strategies to treat NPC. 相似文献
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Circulating Epstein‐Barr virus–encoded micro‐RNAs as potential biomarkers for nasal natural killer/T‐cell lymphoma
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Yuki Komabayashi Kan Kishibe Toshihiro Nagato Seigo Ueda Miki Takahara Yasuaki Harabuchi 《Hematological oncology》2017,35(4):655-663
Nasal natural killer/T‐cell lymphoma (NNKTL) is an Epstein‐Barr virus (EBV)–associated malignancy and is characterized by local invasion and widespread dissemination, with a consequent poor prognosis. Micro‐RNAs (miRNAs) play roles in the pathogenesis of several malignancies by regulating gene expression and have been recently identified as stable entities in serum. Here, we investigated the value of circulating EBV‐miRNAs as biomarkers for NNKTL. Sera of patients with NNKTL were subjected to miRNA polymerase chain reaction (PCR)–array analysis, after which serum EBV‐miRNA levels were verified using quantitative PCR. The latter analysis revealed high miR‐BART2‐5p, miR‐BART7‐3p, miR‐BART13‐3p, and miR‐BART1‐5p expression levels in sera of patients with NNKTL and indicated accurate values for discriminating patients with NNKTL from healthy controls. Levels of these 4 EBV‐miRNAs, which were secreted from NNKTL cells, significantly decreased after treatment compared with those before treatment. Furthermore, a high circulating miR‐BART2‐5p level was associated with disease progression and poor prognosis in patients with NNKTL. Our findings demonstrate that circulating EBV‐miRNAs, particularly miR‐BART2‐5p, may serve as potential diagnostic and prognostic biomarkers in patients with NNKTL. 相似文献
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Tao Yu Lei Liu Jing Li Mingxia Yan Hechun Lin Ying Liu Dandan Chu Hong Tu Aiqin Gu Ming Yao 《Oncotarget》2015,6(30):30239-30250
MicroRNAs (miRNAs) are involved in human cancer including non-small cell lung cancer (NSCLC). In this study, we compared miRNA expression microarray of SPC-A-1sci (high metastatic) and SPC-A-1 (weakly metastatic) cells. We found that miRNA-10a was up-regulated in NSCLC compared with corresponding normal tissues. High expression of miR-10a was associated with tumor node metastasis and lymph node metastasis. Furthermore, overexpression of miR-10a promoted NSCLC cell proliferation, migration and invasion in vitro. We found that PTEN was a direct target of miR-10a in NSCLC. Also miR-10a activated the PTEN/AKT/ERK pathway. We suggest that miR-10a contributes to NSCLC by targeting PTEN. 相似文献
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