Epstein-Barr Virus MicroRNA Expression Increases Aggressiveness of Solid Malignancies

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2015 Sep 17

PMID 26375401

Citations 16

Authors

Deep Pandya

Marisa Mariani

Shiquan He

Mirko Andreoli

Manuela Spennato

Candice Dowell-Martino

Paul Fiedler

Cristiano Ferlini

Affiliations

Soon will be listed here.

Abstract

The Cancer Genome Atlas (TCGA) microRNA (miRNA) initiative has revealed a pivotal role for miRNAs in cancer. Utilizing the TCGA raw data, we performed the first mapping of viral miRNA sequences within cancer and adjacent normal tissues. Results were integrated with TCGA RNA-seq to link the expression of viral miRNAs to the phenotype. Using clinical data and viral miRNA mapping results we also performed outcome analysis. Three lines of evidence lend credence to an active role of viral miRNAs in solid malignancies. First, expression of viral miRNA is consistently higher in cancerous compared to adjacent noncancerous tissues. Second, viral miRNA expression is associated with significantly worse clinical outcome among patients with early stage malignancy. These patients are also featured by increased expression of PD1/PD-L1, a pathway implicated in tumors escaping immune destruction. Finally, a particular cluster of EBV-miRNA (miR-BART2, miR-BART4, miR-BART5, miR-BART18, and miR-BART22) is associated with expression of cytokines known to inhibit host response to cancer. Quantification of specific viral miRNAs may help identify patients who are at risk of poor outcome. These patients may be candidates for novel therapeutic strategies incorporating antiviral agents and/or inhibitors of the PD-1/PD-L1 pathway.

Citing Articles

The role of microRNAs in the gastric cancer tumor microenvironment.

Yu X, Zhang Y, Luo F, Zhou Q, Zhu L Mol Cancer. 2024; 23(1):170.

PMID: 39164671 PMC: 11334576. DOI: 10.1186/s12943-024-02084-x.

Incidental discovery of a Hodgkin lymphoma synchronous to a papillary thyroid carcinoma.

Ben Thayer M, Khanchel F, Helal I, Chiboub D, Lazreg K, Hedhli R Clin Case Rep. 2022; 10(8):e6246.

PMID: 35957786 PMC: 9361809. DOI: 10.1002/ccr3.6246.

Bacterial Diversity Correlates with Overall Survival in Cancers of the Head and Neck, Liver, and Stomach.

Rodriguez R, Menor M, Hernandez B, Deng Y, Khadka V Molecules. 2021; 26(18).

PMID: 34577130 PMC: 8468759. DOI: 10.3390/molecules26185659.

MicroRNA and Other Non-Coding RNAs in Epstein-Barr Virus-Associated Cancers.

Notarte K, Senanayake S, Macaranas I, Albano P, Mundo L, Fennell E Cancers (Basel). 2021; 13(15).

PMID: 34359809 PMC: 8345394. DOI: 10.3390/cancers13153909.

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

De Re V, Caggiari L, De Zorzi M, Fanotto V, Miolo G, Puglisi F Infect Agent Cancer. 2020; 15:42.

PMID: 32582365 PMC: 7310352. DOI: 10.1186/s13027-020-00307-6.

References

Topalian S, Drake C, Pardoll D . Immune checkpoint blockade: a common denominator approach to cancer therapy. Cancer Cell. 2015; 27(4):450-61. PMC: 4400238. DOI: 10.1016/j.ccell.2015.03.001. View

Cortez M, Valdecanas D, Zhang X, Zhan Y, Bhardwaj V, Calin G . Therapeutic delivery of miR-200c enhances radiosensitivity in lung cancer. Mol Ther. 2014; 22(8):1494-1503. PMC: 4435581. DOI: 10.1038/mt.2014.79. View

Diaz-Benitez C, Navarro-Fuentes K, Flores-Sosa J, Juarez-Diaz J, Uribe-Salas F, Roman-Basaure E . CD3zeta expression and T cell proliferation are inhibited by TGF-beta1 and IL-10 in cervical cancer patients. J Clin Immunol. 2009; 29(4):532-44. DOI: 10.1007/s10875-009-9279-7. View

Morin R, OConnor M, Griffith M, Kuchenbauer F, Delaney A, Prabhu A . Application of massively parallel sequencing to microRNA profiling and discovery in human embryonic stem cells. Genome Res. 2008; 18(4):610-21. PMC: 2279248. DOI: 10.1101/gr.7179508. View

Ationu A, Humphries A, Lalloz M, Arya R, Wild B, Warrilow J . Reversal of metabolic block in glycolysis by enzyme replacement in triosephosphate isomerase-deficient cells. Blood. 1999; 94(9):3193-8. View

Marquitz A, Mathur A, Shair K, Raab-Traub N . Infection of Epstein-Barr virus in a gastric carcinoma cell line induces anchorage independence and global changes in gene expression. Proc Natl Acad Sci U S A. 2012; 109(24):9593-8. PMC: 3386136. DOI: 10.1073/pnas.1202910109. View

Mi H, Muruganujan A, Thomas P . PANTHER in 2013: modeling the evolution of gene function, and other gene attributes, in the context of phylogenetic trees. Nucleic Acids Res. 2012; 41(Database issue):D377-86. PMC: 3531194. DOI: 10.1093/nar/gks1118. View

Calin G, Ferracin M, Cimmino A, Di Leva G, Shimizu M, E Wojcik S . A MicroRNA signature associated with prognosis and progression in chronic lymphocytic leukemia. N Engl J Med. 2005; 353(17):1793-801. DOI: 10.1056/NEJMoa050995. View

Croce C . Causes and consequences of microRNA dysregulation in cancer. Nat Rev Genet. 2009; 10(10):704-14. PMC: 3467096. DOI: 10.1038/nrg2634. View

10.

Burke A, Yen T, Shekitka K, Sobin L . Lymphoepithelial carcinoma of the stomach with Epstein-Barr virus demonstrated by polymerase chain reaction. Mod Pathol. 1990; 3(3):377-80. View

11.

. Comprehensive molecular characterization of gastric adenocarcinoma. Nature. 2014; 513(7517):202-9. PMC: 4170219. DOI: 10.1038/nature13480. View

12.

Kroemer G, Galluzzi L, Kepp O, Zitvogel L . Immunogenic cell death in cancer therapy. Annu Rev Immunol. 2012; 31:51-72. DOI: 10.1146/annurev-immunol-032712-100008. View

13.

Nallamshetty S, Chan S, Loscalzo J . Hypoxia: a master regulator of microRNA biogenesis and activity. Free Radic Biol Med. 2013; 64:20-30. PMC: 3762925. DOI: 10.1016/j.freeradbiomed.2013.05.022. View

14.

Elgar G, Vavouri T . Tuning in to the signals: noncoding sequence conservation in vertebrate genomes. Trends Genet. 2008; 24(7):344-52. DOI: 10.1016/j.tig.2008.04.005. View

15.

Flores O, Nakayama S, Whisnant A, Javanbakht H, Cullen B, Bloom D . Mutational inactivation of herpes simplex virus 1 microRNAs identifies viral mRNA targets and reveals phenotypic effects in culture. J Virol. 2013; 87(12):6589-603. PMC: 3676078. DOI: 10.1128/JVI.00504-13. View

16.

Calin G, Croce C . MicroRNA signatures in human cancers. Nat Rev Cancer. 2006; 6(11):857-66. DOI: 10.1038/nrc1997. View

17.

Miller C, Berger J, Mootoor Y, Avdiushko S, Zhu H, Kryscio R . High prevalence of multiple human herpesviruses in saliva from human immunodeficiency virus-infected persons in the era of highly active antiretroviral therapy. J Clin Microbiol. 2006; 44(7):2409-15. PMC: 1489493. DOI: 10.1128/JCM.00256-06. View

18.

Xiao L, Hu Z, Dong X, Tan Z, Li W, Tang M . Targeting Epstein-Barr virus oncoprotein LMP1-mediated glycolysis sensitizes nasopharyngeal carcinoma to radiation therapy. Oncogene. 2014; 33(37):4568-78. PMC: 4162460. DOI: 10.1038/onc.2014.32. View

19.

Pandya D, Mariani M, McHugh M, Andreoli M, Sieber S, He S . Herpes virus microRNA expression and significance in serous ovarian cancer. PLoS One. 2014; 9(12):e114750. PMC: 4259392. DOI: 10.1371/journal.pone.0114750. View

20.

Torres-Poveda K, Burguete-Garcia A, Cruz M, Martinez-Nava G, Bahena-Roman M, Ortiz-Flores E . The SNP at -592 of human IL-10 gene is associated with serum IL-10 levels and increased risk for human papillomavirus cervical lesion development. Infect Agent Cancer. 2012; 7(1):32. PMC: 3552694. DOI: 10.1186/1750-9378-7-32. View