EBV‐miR‐BART12 accelerates migration and invasion in EBV‐associated cancer cells by targeting tubulin polymerization‐promoting protein 1

Wu, Yingfen; Wang, Dan; Fang, Wei; Xiong, Fang; Zhang, Shanshan; Gong, Zhaojian; Shi, Lei; Li, Xiayu; Xiang, Bo; Ma, Jian; Deng, Hao; He, Yi; Liao, Qianjin; Zhang, Wenling; Li, Xiaoling; Li, Yong; Guo, Can; Zeng, Zhaoyang; Li, Guiyuan; Xiong, Wei

doi:10.1096/fj.202001508r

Cited by 19 publications

(19 citation statements)

References 93 publications

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“…As we know, both EBV and human miRNAs play important roles in NPC carcinogenesis and could be drug targets or prognostic biomarkers. The literature review showed that all six miRNAs have been reported to be associated with carcinogenesis in NPC or other cancers (Choi et al, 2013;Liu et al, 2013;Li et al, 2015;Choi and Lee, 2017;Ma et al, 2018;Wu et al, 2020;Jia-Yuan et al, 2020). EBV-encoded miRNA BART12 could promote cell migration and invasion of EBV-associated NPC and gastric cancer by inhibiting TPPP1 mRNA and activating the cellular EMT process (Wu et al, 2020), and miR-BART15-5p could target BRUCE mRNA and TAX1BP1 gene in cancer cells and increase apoptosis and chemosensitivity to 5-FU (Choi et al, 2013;Choi and Lee, 2017).…”

Section: Discussionmentioning

confidence: 99%

Integrative Analysis Identified a 6-miRNA Prognostic Signature in Nasopharyngeal Carcinoma

Chen

Wang

et al. 2021

Front. Cell Dev. Biol.

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BackgroundNasopharyngeal carcinoma (NPC) is an Epstein–Barr virus-associated epithelial malignancy, which is rare in America but endemic in China. The current clinical gold TNM-based standard for prognosis may not be enough. Although some studies have reported that some miRNAs have a prognostic power in NPC, there is a scarcity of independent validation for these miRNAs.MethodsIn this work, we firstly conducted a literature review of all miRNA profiling datasets with survival information, then integrated miRNA expression data across different profiling platforms and built prognostic models using machine learning methods. The Kaplan–Meier method and log-rank tests were applied to estimate correlations of the miRNA signature with survival, and the area under the time-dependent ROC curve (AUC) and concordance index (C-index) were used to assess the predictive power of prognostic models. We also investigated the biological roles of the prognostic miRNAs through identifying their regulated genes and association with immune infiltration.ResultsWe constructed a prognostic model based on 6-miRNA signature (ebv-miR-BART12, ebv-miR-BART15, miR-29c-3p, miR-30e-5p, hsa-miR-375-3p, has-miR-93-5p) using the elastic net penalized Cox regression model. The AUCs of our model predicting 1-, 3-, and 5-year overall survival rates were 0.90, 0.73, and 0.70 for the external validation dataset and showed better prognostic power than models using previously reported miRNA signatures. The 6-miRNA risk score was an independent prognostic predictor for overall survival (OS), disease-free survival (DFS), and metastasis-free survival (MFS). It could stratify patients into low-risk and high-risk groups; patients in the low-risk group treated with concurrent chemotherapy had a better survival. On the basis that the 6-miRNA risk score improved the current clinical gold standard for prognosis, we built a nomogram integrating both clinical characterizations and the risk score to predict 3-, 5-, and 10-year overall survival. Functional analysis suggested that the six miRNAs mainly play roles in virus infection pathways and oncogenic signaling pathways and associated with B-cell expression.ConclusionWe identified a 6-miRNA prognostic signature in nasopharyngeal carcinoma across miRNA profiling platforms and patient geographical difference, which showed good prediction capability in terms of OS, DFS, and MFS. The 6-miRNA risk score might be helpful for clinicians to make treatment strategies and predict patient outcomes.

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Section: Discussionmentioning

confidence: 99%

Integrative Analysis Identified a 6-miRNA Prognostic Signature in Nasopharyngeal Carcinoma

Chen

Wang

et al. 2021

Front. Cell Dev. Biol.

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“…During EET, tumor cells lose their polarity and tight junctions, and gain the ability to infiltrate and migrate. This process is accompanied by the transition from epithelial marker molecules to endothelial marker molecules, such as decreased expression of tight junction proteins such as E-cadherin and occludin, and increased expression of vimentin, VE-cadherin (adhesion molecule of endothelial cells), fibronectin, vitronectin, and other molecules [106,107]. Among these, E-cadherin is a tight junction protein between epithelial cells, and its expression is significantly downregulated in VM [108].…”

Section: Hypoxia Promotes Vasculogenic Mimicry By Facilitating Epithementioning

confidence: 99%

“…HIF-1 can bind to the hypoxia response element (HRE) on the Twist, Snail, and ZEB2 promoter sequences in the nucleus to play a regulatory role [118][119][120]. Twist protein, a helix-loop-helix transcription factor, belonging to the bHLH transcription factor family, is encoded by the Twist gene located on human chromosome 7p21, and contains two transcription factors, Twist1 and Twist2 [107]. TWIST expression can downregulate the expression of multiple epithelial genes and activate the expression of endothelial genes [106].…”

Section: Hypoxia Promotes Vasculogenic Mimicry By Facilitating Epithementioning

confidence: 99%

Mechanisms of vasculogenic mimicry in hypoxic tumor microenvironments

et al. 2021

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Background Vasculogenic mimicry (VM) is a recently discovered angiogenetic process found in many malignant tumors, and is different from the traditional angiogenetic process involving vascular endothelium. It involves the formation of microvascular channels composed of tumor cells; therefore, VM is considered a new model for the formation of new blood vessels in aggressive tumors, and can provide blood supply for tumor growth. Many studies have pointed out that in recent years, some clinical treatments against angiogenesis have not been satisfactory possibly due to the activation of VM. Although the mechanisms underlying VM have not been fully elucidated, increasing research on the soil “microenvironment” for tumor growth suggests that the initial hypoxic environment in solid tumors is inseparable from VM. Main body In this review, we describe that the stemness and differentiation potential of cancer stem cells are enhanced under hypoxic microenvironments, through hypoxia-induced epithelial-endothelial transition (EET) and extracellular matrix (ECM) remodeling to form the specific mechanism of vasculogenic mimicry; we also summarized some of the current drugs targeting VM through these processes, suggesting a new reference for the clinical treatment of tumor angiogenesis. Conclusion Overall, the use of VM inhibitors in combination with conventional anti-angiogenesis treatments is a promising strategy for improving the effectiveness of targeted angiogenesis treatments; further, considering the importance of hypoxia in tumor invasion and metastasis, drugs targeting the hypoxia signaling pathway seem to achieve good results.

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“…The ability of single-cell gene expression profiling to identify specific patterns of gene expression allows for the elucidation of mechanisms underlying tumor invasion and metastasis [102][103][104][105] that are critical for preventing the spread of cancer, which considerably complicates treatment (Table 2 (see Additional file 3)).…”

Section: Discovery Of Invasion and Metastasis Mechanismsmentioning

confidence: 99%

What are the applications of single-cell RNA sequencing in cancer research: a systematic review

Xiong

Wang

et al. 2021

J Exp Clin Cancer Res

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Single-cell RNA sequencing (scRNA-seq) is a tool for studying gene expression at the single-cell level that has been widely used due to its unprecedented high resolution. In the present review, we outline the preparation process and sequencing platforms for the scRNA-seq analysis of solid tumor specimens and discuss the main steps and methods used during data analysis, including quality control, batch-effect correction, normalization, cell cycle phase assignment, clustering, cell trajectory and pseudo-time reconstruction, differential expression analysis and gene set enrichment analysis, as well as gene regulatory network inference. Traditional bulk RNA sequencing does not address the heterogeneity within and between tumors, and since the development of the first scRNA-seq technique, this approach has been widely used in cancer research to better understand cancer cell biology and pathogenetic mechanisms. ScRNA-seq has been of great significance for the development of targeted therapy and immunotherapy. In the second part of this review, we focus on the application of scRNA-seq in solid tumors, and summarize the findings and achievements in tumor research afforded by its use. ScRNA-seq holds promise for improving our understanding of the molecular characteristics of cancer, and potentially contributing to improved diagnosis, prognosis, and therapeutics.

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EBV‐miR‐BART12 accelerates migration and invasion in EBV‐associated cancer cells by targeting tubulin polymerization‐promoting protein 1

Cited by 19 publications

References 93 publications

Integrative Analysis Identified a 6-miRNA Prognostic Signature in Nasopharyngeal Carcinoma

Integrative Analysis Identified a 6-miRNA Prognostic Signature in Nasopharyngeal Carcinoma

Mechanisms of vasculogenic mimicry in hypoxic tumor microenvironments

What are the applications of single-cell RNA sequencing in cancer research: a systematic review

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