Tu192 - Alterations in Circular RNA Landscape in Septic Peripheral Blood Mononuclear Cells Before and After Intensive Care

Frank Yu – Physiology and Pharmacology – University of Western Ontario; Ayesha Warsi – Schulich School of Medicine and Dentistry – University of Western Ontario; Kassie Rong – Pathology and Laboratory Medicine – University of Western Ontario; Tina Mele, MD, PhD, FRCSC, FACS – Associate Professor, Surgery, University of Western Ontario; Xiufen Zheng, PhD – Associate Professor, Pathology and Laboratory Medicine, University of Western Ontario

Abstract Text: Sepsis, the leading cause of death in intensive care units (ICU), is associated with alterations in genomic expression in leukocytes. Understanding of molecular mechanisms and current treatments for sepsis remain to be improved. Circular RNAs (circRNAs) are a novel class of non-coding RNA that is increasing shown to participate in complex pathologies. We hypothesized that circular RNAs in peripheral blood mononuclear cells (PBMCs) actively mediate the pathogenesis of sepsis.

PBMCs were isolated from three sepsis patients before and after intensive care, and RNA sequencing was conducted with total RNA. CircRNAs were identified using four annotation pipelines and their expression was compared. Expression of circular RNA ASPH (circASPH), the most differentially expressed circRNA, was validated through quantitative PCR in a larger sample size. In silico analysis was conducted to predict potential interactions with mRNAs and RNA binding proteins (RBPs).

Overall circRNA expression in septic PBMCs were found to be more abundant and less diverse at ICU admission (ICU-AD) compared with ICU discharge (ICU-DC). We identified 938 circRNA species, with 34 differentially expressed between ICU-AD and ICU-DC. CircASPH was found to be highly expressed at ICU-AD, its level positively correlated with the length of stay in ICU. CircASPH was predicted to bind four microRNAs including miR-670, miR-7975, miR-6818 and miR-384 and interact with proteins TLR2 and ZC3H12D. This study characterized differential expression of circRNA in septic PBMCs between ICU admission and discharge and explored their potential role as novel markers or targets for treatment of sepsis.