Abstract

Circular RNAs (circRNAs) may be potential biomarkers or therapeutic targets of hemophagocytic syndrome (HPS) due to their high stability, covalently closed structure and implicated roles in gene regulation. The aim of the present study was to determine and characterize the circRNAs from natural killer (NK)/T-cell lymphoma-associated hemophagocytic syndrome (NK/T-LAHS). CircRNA in NK/T-LAHS and healthy control patient serum were assessed using next-generation sequencing (NGS). One hundred and forty-three differentially expressed circRNAs of which 114 were up-regulated and 29 were down-regulated in NK/T-LAHS patients were identified. Next, Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses to explore the roles of these circRNAs were utilized, and a microRNA (miRNA) target gene prediction software to predict the interaction of circRNAs and miRNAs was used. Moreover, five circRNAs were then selected as NK/T-LAHS candidate circRNAs which were related to tumors and contained NK/T-LAHS-related miRNA-binding sites. Using real-time PCR, the significant up-regulation of these five circRNAs in NK/T-LAHS patient serum were verified. Together these results show that circRNAs may serve as valuable diagnostic biomarkers of early NK/T-LAHS, with potential therapeutic targets in disease progression.

Highlights

  • Hemophagocytic lymphohistiocytosis (HLH), called hemophagocytic syndrome (HPS), is a potentially life-threatening disease characterized by impaired natural killer (NK) and cytotoxic T-cell function, cytokine storm and overwhelming inflammation [1,2]

  • There are no biomarkers of NK/T-lymphoma-associated hemophagocytic syndrome (LAHS) sensitive enough for diagnostic purposes

  • This marker can sensitively and effectively diagnose early NK / T-LAHS, which will be confirmed in further studies

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Summary

Introduction

Hemophagocytic lymphohistiocytosis (HLH), called hemophagocytic syndrome (HPS), is a potentially life-threatening disease characterized by impaired natural killer (NK) and cytotoxic T-cell function, cytokine storm and overwhelming inflammation [1,2]. Circular RNA (circRNA) is a novel molecule that is formed by a covalently closed loop with different sizes and sources and represents a class of abundant, stable and widely existing RNA molecules in animals [7,8]. It plays an important role in biological processes (BPs). CircRNA interacts with disease-related miRNA through a competitive endogenous RNA (ceRNA) mechanism, and plays an important regulatory role in disease[11,12]. The role of circRNA in NK/T-cell lymphoma-related hemophagocytic syndrome has not been determined

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