EBV-miR-BART7-3p Imposes Stemness in Nasopharyngeal Carcinoma Cells by Suppressing SMAD7

Cai, Longmei; Long, Yun; Chong, Tuotuo; Cai, Wenzhi; Tsang, Chi Man; Zhou, Xiaohan; Lin, Yanling; Ding, Tengteng; Zhou, Wenyan; Zhao, Hongli; Chen, Yuxiang; Wang, Jianguo; Lyu, Xiaoming; Cho, William C.; Li, Xin

doi:10.3389/fgene.2019.00939

Cited by 30 publications

(24 citation statements)

References 42 publications

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“… 15 Numbers of studies have shown that NPC is closely associated with EBV infection. 16 , 17 , 18 , 19 It was found that EBV-coded miRNAs, such as EBV-miR-BART1, 20 BART2-5p, 21 BART7, 22 and BART13, 23 are involved in tumorigenesis and NPC progression, and could be used as biomarkers or prognostic indicators. In a prior study, we found that EBV-miR-BART22 has a high expression level in NPC.…”

Section: Introductionmentioning

confidence: 99%

miR-4721, Induced by EBV-miR-BART22, Targets GSK3β to Enhance the Tumorigenic Capacity of NPC through the WNT/β-catenin Pathway

Tang

Chen

et al. 2020

Molecular Therapy - Nucleic Acids

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Nasopharyngeal carcinoma (NPC) is prevalent in East and Southeast Asia. In a previous study, Epstein-Barr virus (EBV)-miR-BART22 induces tumor metastasis and stemness and is significantly involved in NPC progression. In the present study, we observed that miR-4721 is induced by EBV-miR-BART22 through phosphatidylinositol 3-kinase (PI3K)/AKT/c-JUN/Sp1 signaling to promote its transcription. In a subsequent study, we observed that miR-4721 serves as a potential oncogenic factor promoting NPC cell cycle progression and cell proliferation in vitro and in vivo . Mechanism analysis indicated that miR-4721 directly targetes GSK3β and reduces its expression, which therefore elevates β-catenin intra-nuclear aggregation and activates its downstream cell cycle factors, including CCND1 and c-MYC. In clinical samples, miR-4721 and GSK3β are respectively observed to be upregulated and downregulated in NPC progression. Elevated expression of miR-4721 is positively associated with clinical progression and poor prognosis. Our study first demonstrated that miR-4721 as an oncogene is induced by EBV-miR-BART22 via modulating PI3K/AKT/c-JUN/Sp1 signaling to target GSK3β, which thus activates the WNT/β-catenin-stimulated cell cycle signal and enhances the tumorigenic capacity in NPC. miR-4721 may be a potential biomarker or therapeutic target in NPC treatment in the future.

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Section: Introductionmentioning

confidence: 99%

miR-4721, Induced by EBV-miR-BART22, Targets GSK3β to Enhance the Tumorigenic Capacity of NPC through the WNT/β-catenin Pathway

Tang

Chen

et al. 2020

Molecular Therapy - Nucleic Acids

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“…Based on these reports, both EBV-miR-BART1, and EBV-miR-BART7-3p have been shown to induce tumor metastasis by regulating various kinds of pathways in NPC [7,15]. We further discovered that EBV-miR-BART7-3p increased the chemoresistance of NPC [16]. With the development of the research of BARTs, we began to explore the bridge between the treatment of resistance and metastasis.…”

Section: Discussionmentioning

confidence: 99%

EBV Encoded miRNA BART8-3p Drives Radioresistance-Associated Metastasis in Nasopharyngeal Carcinoma

Zhou

Lin

Chen

et al. 2020

Preprint

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Background: Radiotherapy plays an important role in the treatment of nasopharyngeal carcinoma (NPC), however, 20 % of patients with NPC exhibit unusual radioresistance. Patients with radioresistance are at risk of recurrence, so it is imperative to explore the mechanism of resistance to radiotherapy. In the past, studies on the mechanism of radioresistance have been restricted to DNA damage and related cell cycle remodeling or apoptosis. So far, no studies have explored the relationship between radioresistance and metastasis. Methods: We analyzed the metastasis rate of patients with recurrent NPC and that of patients with primary NPC. Constructing an acquired radioresistant NPC cell line and detect their metastatic ability in vivo and in vitro. RNA-deep sequencing was performed to predict the targeted host genes of EBV-miR-BART8-3p. Western blotting, real-time PCR and immunochemistry were conducted to investigate the relationship of clinicopathologic features and EBV-miR-BART8-3p or PAG1. Results:Through the analysis of clinical samples, we observed that the metastasis rate of recurrent NPC was much higher than that of primary patients. In vitro and in vivo experiments showed that NPC cells with acquired radioresistance exhibited a stronger ability for invasion and metastasis. Mechanistically, we found that the Epstein–Barr virus (EBV)-encoded miRNA BART8-3p was increased in patients with NPC and its expression was positively correlated with adverse prognostic factors, such as radioresistance. Besides, miR-BART8-3p promoted the epithelial-mesenchymal transition (EMT), invasion, and metastasis of radioresistant NPC cells by targeting and inhibiting their PAG1 host gene. Conclusion: These results demonstrated a correlation between radioresistance and metastasis in NPC, which depended on the elevated levels of the EBV-encoded miRNA BART8-3p and the inhibition of the PAG1 host gene. These findings suggested a novel role for EBV-miR-BART8-3p and PAG1 in recurrence NPC and highlighted their potential value as prognostic indicators or therapeutic targets.

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“…miR-BART7-3p has been hypothesized to play a role in tumor growth and invasion through the suppression of phosphatase and tensin homolog (PTEN) protein and others against decapentaplegic homolog 7 (SMAD7) [57,58]. PTEN is one of the main tumor suppressor genes involved in the regulation of the cell cycle.…”

Section: Bart Mirnas In Gastric Cancermentioning

confidence: 99%

Epstein-Barr virus BART microRNAs in EBV- associated Hodgkin lymphoma and gastric cancer

Caggiari

Zorzi

et al. 2020

Infect Agents Cancer

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Background: EBV produces miRNAs with important functions in cancer growth, tumor invasion and host immune surveillance. The discovery of EBV miR-BARTs is recent, and most of their functions are still unknown. Nonetheless, some new studies underline their key roles in EBV-associated malignancies. Main body: In EBV-associated tumors, the expression profile of miR-BARTs varies according to the cell type, autophagic process and signals received from the tumor microenvironment. By the same way of interest is the interaction between tumor cells and the tumor environment by the release of selected EBV miR-BARTs in addition to the tumor proteins trough tumor exosomes. Conclusion: In this review, we discuss new findings regarding EBV miR-BARTs in Hodgkin lymphoma and gastric cancer. The recent discovery that miRNAs are released by exosomes, including miR-BARTs, highlights the importance of tumor and microenvironment interplay with more specific effects on the host immune response.

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EBV-miR-BART7-3p Imposes Stemness in Nasopharyngeal Carcinoma Cells by Suppressing SMAD7

Cited by 30 publications

References 42 publications

miR-4721, Induced by EBV-miR-BART22, Targets GSK3β to Enhance the Tumorigenic Capacity of NPC through the WNT/β-catenin Pathway

miR-4721, Induced by EBV-miR-BART22, Targets GSK3β to Enhance the Tumorigenic Capacity of NPC through the WNT/β-catenin Pathway

EBV Encoded miRNA BART8-3p Drives Radioresistance-Associated Metastasis in Nasopharyngeal Carcinoma

Epstein-Barr virus BART microRNAs in EBV- associated Hodgkin lymphoma and gastric cancer

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