Epstein-Barr Virus_Encoded LMP1 Upregulates MicroRNA-21 to Promote the Resistance of Nasopharyngeal Carcinoma Cells to Cisplatin-Induced Apoptosis by Suppressing PDCD4 and Fas-L

Yang, Guang; Huang, Tie Jun; Li, Peng; Yang, Chang Fu; Liu, Ran Yi; Hong, Huixiao; Chu, Qiao Qiao; Yang, Hong; Huang, Junting; Zhu, Zhen; Qian, Chao Nan; Huang, Bi

doi:10.1371/journal.pone.0078355

Cited by 76 publications

(61 citation statements)

References 59 publications

(86 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…MIR155 is essential for LCL proliferation. EBV super-enhancers, enriched with EBNA2, EBNALP, and LMP1-activated NF-κB subunits up regulate MIR155 and MIR21 expression in LCLs (Rosato et al, 2012; Yang et al, 2013). MIR21 regulates PTEN.…”

Section: Discussionmentioning

confidence: 99%

Epstein-Barr Virus Oncoprotein Super-enhancers Control B Cell Growth

Zhou

Schmidt

Jiang

et al. 2015

Cell Host & Microbe

163

222

View full text Add to dashboard Cite

Summary Super-enhancers are clusters of gene-regulatory sites bound by multiple transcription factors that govern cell transcription, development, phenotype, and oncogenesis. By examining Epstein-Barr virus (EBV) transformed lymphoblastoid cell lines (LCLs), we identified four EBV oncoproteins and five EBV-activated NF-κB subunits co-occupying ~1800 enhancer sites. Of these, 187 had markedly higher and broader histone H3K27ac signals characteristic of super-enhancers, and were designated “EBV super-enhancers”. EBV super-enhancer-associated genes included the MYC and BCL2 oncogenes, enabling LCL proliferation and survival. EBV super-enhancers were enriched for B cell transcription factor motifs and had a high co-occupancy of the transcription factors STAT5 and NFAT. EBV super-enhancer-associated genes were more highly expressed than other LCL genes. Disrupting EBV super-enhancers by the bromodomain inhibitor, JQ1 or conditionally inactivating an EBV oncoprotein or NF-κB decreased MYC or BCL2 expression and arrested LCL growth. These findings provide insight into mechanisms of EBV-induced lymphoproliferation and identify potential therapeutic interventions.

show abstract

Section: Discussionmentioning

confidence: 99%

Epstein-Barr Virus Oncoprotein Super-enhancers Control B Cell Growth

Zhou

Schmidt

Jiang

et al. 2015

Cell Host & Microbe

163

222

View full text Add to dashboard Cite

show abstract

“…For example, miR-155 is upregulated by EBV infection (40,46), miR-21 is upregulated by EBV (40,47) and hepatitis C virus infection (48), and miR-17, miR-20, miR-96, miR-182, and miR-183 are upregulated, while miR-21, miR-99, miR-100, and miR-101 are downregulated by HCMV infection (41,(49)(50)(51).…”

mentioning

confidence: 99%

MicroRNA miR-21 Attenuates Human Cytomegalovirus Replication in Neural Cells by Targeting Cdc25a

Liu

et al. 2015

J Virol

View full text Add to dashboard Cite

Congenital human cytomegalovirus (HCMV) infection is a leading cause of birth defects, primarily manifesting as neurological disorders. HCMV infection alters expression of cellular microRNAs (miRs These results suggest that Cdc25a promotes HCMV replication and elevation of Cdc25a levels after HCMV infection are due in part to HCMV-mediated repression of miR-21. Thus, miR-21 is an intrinsic antiviral factor that is modulated by HCMV infection. This suggests a role for miR-21 downregulation in the neuropathogenesis of HCMV infection of the developing CNS. IMPORTANCEHuman cytomegalovirus (HCMV) is a ubiquitous pathogen and has very high prevalence among population, especially in China, and congenital HCMV infection is a major cause for birth defects. Elucidating virus-host interactions that govern HCMV replication in neuronal cells is critical to understanding the neuropathogenesis of birth defects resulting from congenital infection. In this study, we confirm that HCMV infection downregulates miR-21 but upregulates Cdc25a. Further determined the negative effects of cellular miRNA miR-21 on HCMV replication in neural progenitor/stem cells and U-251MG glioblastoma/astrocytoma cells. More importantly, our results provide the first evidence that miR-21 negatively regulates HCMV replication by targeting Cdc25a, a vital cell cycle regulator. We further found that viral gene products of IE1, pp71, and UL26 play roles in inhibiting miR-21 expression, which in turn causes increases in Cdc25a and benefits HCMV replication. Thus, miR-21 appears to be an intrinsic antiviral factor that represents a potential target for therapeutic intervention.

show abstract

“…Among them was the research conducted by Meng et al 21 showed that PTEN (Phosphatase and tensin homolog) was a direct target of microRNA-21 that contribute to cell invasion. MicroRNA-21 contributes to apoptotic and chemotherapy resistance by directly targeting PDCD4 22 .…”

Section: Discussionmentioning

confidence: 99%

Expression of Micro RNA-21 and 29c in Blood Plasma of Patients with Nasopharyngeal Carcinoma

Savitri¹,

Safri²,

Djamin³

et al. 2017

J. of Medical Sciences

View full text Add to dashboard Cite

MicroRNA (miRNA) are small non-coding RNA molecules that work in post-transcription and can cause degradation and cell damage through the targeted gene. Damage to these cells influences the process of carcinogenesis. One of them is in nasopharyngeal carcinoma (NPC). Among families of miRNA that play a role in the pathogenesis of NPC that miRNA-21, miRNA-29c and which is closely associated with the progression, invasion and tumor metastasis. The purpose of this study was to determine the expression of miRNA-21 and miRNA-29c. Knowledge of these miRNA could help in the development of targeted therapy in carcinoma, as a biomarker diagnostic and clinical predictive and would be useful in therapeutic decision making. The research design was observational analytic study carried out in Wahidin Sudirohusodo Makassar, January-June, 2017. The collected blood plasma was isolated and then synthesized to cDNA and calculated quantitatively with qRT-PCR and analyzed using CFX manager 96. There were 52 samples consisting of 27 plasma NPC and 25 controls. From the plasma detected miRNA-21 and miRNA-29c. Expression of miRNA-21 increased 4.47795 fold compared with controls (p<0.05)) but its expression can not describe the progression of the tumor at a later stadium (p<0.05). In contrast, the expression of miRNA-29c decreased -119.317 fold compared with control, its regulation at a later stadium did not change significantly. Both miRNA-21 and miRNA-29c in blood plasma can use for NPC detection but a single microRNA examination is less able to provide an overview of progressivity.

show abstract

Epstein-Barr Virus_Encoded LMP1 Upregulates MicroRNA-21 to Promote the Resistance of Nasopharyngeal Carcinoma Cells to Cisplatin-Induced Apoptosis by Suppressing PDCD4 and Fas-L

Cited by 76 publications

References 59 publications

Epstein-Barr Virus Oncoprotein Super-enhancers Control B Cell Growth

Epstein-Barr Virus Oncoprotein Super-enhancers Control B Cell Growth

MicroRNA miR-21 Attenuates Human Cytomegalovirus Replication in Neural Cells by Targeting Cdc25a

Expression of Micro RNA-21 and 29c in Blood Plasma of Patients with Nasopharyngeal Carcinoma

Contact Info

Product

Resources

About