title: Cellular and viral microRNAs in sepsis: mechanisms of action and clinical applications.
abstract: Regardless of its etiology, once septic shock is established, survival rates drop by 7.6% for every hour antibiotic therapy is delayed. The early identification of the cause of infection and prognostic stratification of patients with sepsis are therefore important clinical priorities. Biomarkers are potentially valuable clinical tools in this context, but to date, no single biomarker has been shown to perform adequately. Hence, in an effort to discover novel diagnostic and prognostic markers in sepsis, new genomic approaches have been employed. As a result, a number of small regulatory molecules called microRNAs (miRNAs) have been identified as key regulators of the inflammatory response. Although deregulated miRNA expression is increasingly well described, the pathophysiological roles of these molecules in sepsis have yet to be fully defined. Moreover, non-human miRNAs, including two Kaposi Sarcoma herpesvirus-encoded miRNAs, are implicated in sepsis and may drive enhanced secretion of pro-inflammatory and anti-inflammatory cytokines exacerbating sepsis. A better understanding of the mechanism of action of both cellular and viral miRNAs, and their interactions with immune and inflammatory cascades, may therefore identify novel therapeutic targets in sepsis and make biomarker-guided therapy a realistic prospect.
authors.affiliation: Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Dana Elena
authors.initials: DE
authors.lastname: Giza
authors.affiliation: Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Enrique
authors.initials: E
authors.lastname: Fuentes-Mattei
authors.affiliation: Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.|Department of Surgery, University Hospital Southampton, Southampton, UK.
authors.forename: Marc David
authors.initials: MD
authors.lastname: Bullock
authors.affiliation: Department of Surgery, Fundeni Clinical Hospital, Bucharest, Romania.
authors.forename: Stefan
authors.initials: S
authors.lastname: Tudor
authors.affiliation: Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.|College of Science, Chemistry and Philosophy, University of Notre Dame, Notre Dame, IN, USA.
authors.forename: Matthew Joseph
authors.initials: MJ
authors.lastname: Goblirsch
authors.affiliation: Children's Center for Cancer and Blood Diseases and The Saban Research Institute, Children's Hospital Los Angeles, Los Angeles, CA, USA.|Department of Pediatrics and Department of Molecular Microbiology & Immunology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: Muller
authors.initials: M
authors.lastname: Fabbri
authors.affiliation: Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, USA.
authors.forename: Florea
authors.initials: F
authors.lastname: Lupu
authors.affiliation: Department of Emergency Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.|Department of Endocrine Neoplasia and Hormonal Disorders, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Sai-Ching Jim
authors.initials: SJ
authors.lastname: Yeung
authors.affiliation: Department of Surgery, Fundeni Clinical Hospital, Bucharest, Romania.|UMF Carol Davila, Bucharest, Romania.
authors.forename: Catalin
authors.initials: C
authors.lastname: Vasilescu
authors.affiliation: Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.|RNA Interference and Non-Coding RNA Center, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: George Adrian
authors.initials: GA
authors.lastname: Calin
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002986:Clinical Trials as Topic; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism*; D018716:Molecular Mimicry; D018805:Sepsis / Q000235:genetics* / Q000276:immunology; D014780:Viruses / Q000235:genetics*
chemical_list: D015415:Biomarkers; D035683:MicroRNAs