title: Cellular and Kaposi's sarcoma-associated herpes virus microRNAs in sepsis and surgical trauma.
abstract: Once a patient is in septic shock, survival rates drop by 7.6% for every hour of delay in antibiotic therapy. Biomarkers based on the molecular mechanism of sepsis are important for timely diagnosis and triage. Here, we study the potential roles of a panel of cellular and viral miRNAs as sepsis biomarkers. We performed genome-wide microRNA (miRNA) expression profiling in leukocytes from septic patients and nonseptic controls, combined with quantitative RT-PCR in plasmas from two cohorts of septic patients, two cohorts of nonseptic surgical patients and healthy volunteers. Enzyme-linked immunosorbent assay, miRNA transfection and chromatin immunoprecipitation were used to study the effects of Kaposi sarcoma herpes virus (KSHV) miRNAs on interleukin's secretion. Differences related to sepsis etiology were noted for plasma levels of 10 cellular and 2 KSHV miRNAs (miR-K-10b and miR-K-12-12*) between septic and nonseptic patients. All the sepsis groups had high KSHV miRNAs levels compared with controls; Afro-American patients had higher levels of KSHV-miR-K12-12* than non-Afro-American patients. Both KSHV miRNAs were increased on postoperative day 1, but returned to baseline on day 7; they acted as direct agonists of Toll-like receptor 8 (TLR8), which might explain the increased secretion of the IL-6 and IL-10. Cellular and KSHV miRNAs are differentially expressed in sepsis and early postsurgical patients and may be exploited for diagnostic and therapeutic purposes. Increased miR-K-10b and miR-K12-12* are functionally involved in sepsis as agonists of TLR8, forming a positive feedback that may lead to cytokine dysregulation.
authors.affiliation: 1] Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA [2] Department of Surgery, Fundeni Clinical Hospital, Bucharest, Romania.
authors.forename: S
authors.initials: S
authors.lastname: Tudor
authors.affiliation: 1] Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA [2] Department of Surgery, Fundeni Clinical Hospital, Bucharest, Romania.
authors.forename: D E
authors.initials: DE
authors.lastname: Giza
authors.affiliation: Department of Biostatistics, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: H Y
authors.initials: HY
authors.lastname: Lin
authors.affiliation: Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: L
authors.initials: L
authors.lastname: Fabris
authors.affiliation: Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: K
authors.initials: K
authors.lastname: Yoshiaki
authors.affiliation: Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: L
authors.initials: L
authors.lastname: D'Abundo
authors.affiliation: Department of Pharmacy, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: K M
authors.initials: KM
authors.lastname: Toale
authors.affiliation: Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: M
authors.initials: M
authors.lastname: Shimizu
authors.affiliation: Laboratory for Technologies of Advanced Therapies and Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Ferracin
authors.affiliation: Departments of Pediatrics and Molecular Microbiology & Immunology, University of Southern California, Keck School of Medicine, Norris Comprehensive Cancer Center, Children's Center for Cancer and Blood Diseases, Children's Hospital Los Angeles, Los Angeles, CA, USA.
authors.forename: K B
authors.initials: KB
authors.lastname: Challagundla
authors.affiliation: Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: M Angelica
authors.initials: MA
authors.lastname: Cortez
authors.affiliation: Department of Molecular and Cellular Oncology, Molecular Genetics of Cancer Training Program, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: E
authors.initials: E
authors.lastname: Fuentes-Mattei
authors.affiliation: Intensive Care Unit and Department of Anesthesiology, Fundeni Clinical Hospital, Bucharest, Romania.
authors.forename: D
authors.initials: D
authors.lastname: Tulbure
authors.affiliation: Department of Emergency Medicine, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: C
authors.initials: C
authors.lastname: Gonzalez
authors.affiliation: Department of Emergency Medicine, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: J
authors.initials: J
authors.lastname: Henderson
authors.affiliation: Department of Emergency Medicine, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: M
authors.initials: M
authors.lastname: Row
authors.affiliation: Department of Emergency Medicine, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: T W
authors.initials: TW
authors.lastname: Rice
authors.affiliation: The Center for RNA Interference and Non-coding RNAs, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: C
authors.initials: C
authors.lastname: Ivan
authors.affiliation: Laboratory for Technologies of Advanced Therapies and Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Negrini
authors.affiliation: Departments of Pediatrics and Molecular Microbiology & Immunology, University of Southern California, Keck School of Medicine, Norris Comprehensive Cancer Center, Children's Center for Cancer and Blood Diseases, Children's Hospital Los Angeles, Los Angeles, CA, USA.
authors.forename: M
authors.initials: M
authors.lastname: Fabbri
authors.affiliation: Department of Biostatistics, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: J S
authors.initials: JS
authors.lastname: Morris
authors.affiliation: 1] Department of Emergency Medicine, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA [2] Department of Endocrine Neoplasia and Hormonal Disorders, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: S-C J
authors.initials: SC
authors.lastname: Yeung
authors.affiliation: Department of Surgery, Fundeni Clinical Hospital, Bucharest, Romania.
authors.forename: C
authors.initials: C
authors.lastname: Vasilescu
authors.affiliation: 1] Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA [2] The Center for RNA Interference and Non-coding RNAs, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: G A
authors.initials: GA
authors.lastname: Calin
mesh_terms: D018806:APACHE; D001741:Black or African American; D000368:Aged; D016022:Case-Control Studies; D025461:Feedback, Physiological; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D019288:Herpesvirus 8, Human / Q000235:genetics*; D006801:Humans; D015850:Interleukin-6 / Q000097:blood / Q000235:genetics; D016209:Interleukin-8 / Q000097:blood / Q000235:genetics; D007963:Leukocytes, Mononuclear / Q000378:metabolism / Q000473:pathology / Q000821:virology; D008297:Male; D035683:MicroRNAs / Q000097:blood / Q000235:genetics*; D008875:Middle Aged; D012514:Sarcoma, Kaposi / Q000097:blood / Q000208:ethnology / Q000235:genetics* / Q000401:mortality; D018805:Sepsis / Q000097:blood / Q000208:ethnology / Q000235:genetics* / Q000401:mortality; D015398:Signal Transduction; D016019:Survival Analysis; D051200:Toll-Like Receptor 8 / Q000097:blood / Q000235:genetics*; D014947:Wounds and Injuries / Q000097:blood / Q000208:ethnology / Q000235:genetics* / Q000401:mortality
chemical_list: C508600:IL6 protein, human; D015850:Interleukin-6; D016209:Interleukin-8; D035683:MicroRNAs; C495349:TLR8 protein, human; D051200:Toll-Like Receptor 8