Non-coding RNA: a potential biomarker and therapeutic target for sepsis

Abstract

Sepsis, a syndrome of physiologic, pathologic, and biochemical abnormalities caused by an altered systemic host response to infection, has become the main cause of death among patients admitted to the intensive care units. Recently, genome-wide expression analysis revealed that over 80% of the essential genetic elements were altered in critically ill patients. Notably, non-coding RNAs, including microRNAs, long non-coding RNAs and circular RNAs, have been proven to play essential roles in innate immunity, mitochondrial dysfunction and organ dysfunction. In this review, we introduced the biogenesis of non-coding RNAs briefly and summed up different kinds of non-coding RNAs in regulation of sepsis, which could provide a more comprehensive understanding about pathogenesis of the disease. Additionally, we summarized the limitations of current biomarkers and then recommended some non-coding RNAs as novel potential biomarkers for sepsis and sepsis-induced organ dysfunction. Besides, we also introduced some problems and challenges that need to be overcome during the clinical application of non-coding RNAs. Future research should focus on elucidating their molecular mechanisms, particularly long non-coding RNAs as well as circular RNAs and sepsis, to further understanding of the disease process. With the in-depth understanding of the mechanism of sepsis, non-coding RNAs provide a new insight into sepsis and could become the novel therapeutic targets in the future.

Elevated circulating lnc‐ANRIL/miR‐125a axis level predicts higher risk, more severe disease condition, and worse prognosis of sepsis

“…Recently, the wide application of high‐throughput sequencing benefiting from the progress in technology and decrease in cost has led to incremental improvements in the exploration of sepsis pathogenesis, among which noncoding RNA takes a critical place in the participation of inflammation, immune disorder, and organ dysfunction in sepsis . With respect to the values of noncoding RNAs to be biomarkers or therapeutic targets in sepsis patients, long noncoding RNA (lncRNA) and microRNA (miRNA) are the most implicated ones . Lnc‐antisense noncoding RNA in the INK4 locus (ANRIL) is a lncRNA located on chromosome 9p21 region and transcribed by RNA polymerase II and is indicated in the regulation of inflammation and immune responses .…”

“…[7][8][9][10] With respect to the values of noncoding RNAs to be biomarkers or therapeutic targets in sepsis patients, long noncoding RNA (lncRNA) and microRNA (miRNA) are the most implicated ones. 11,12 Lnc-antisense noncoding RNA in the INK4 locus (ANRIL) is a lncRNA located on chromosome 9p21 region and transcribed by RNA polymerase II and is indicated in the regulation of inflammation and immune responses. 13,14 miR-125a, a highly reserved miRNA locating on chromosome 19, 11, and 21, is also closely related to inflammation and immunity, and this miRNA has been reported to have the potential in regulating sepsis pathogenesis.…”

The predictive value of microRNA‐21 for sepsis risk and its correlation with disease severity, systemic inflammation, and 28‐day mortality in sepsis patients

“…As a major public health problem, sepsis is the leading cause of death among patients admitted to the intensive care units. And sepsis survivors experience physical limitations, cognitive impairment, and mental health impairment after discharge . Therefore, it is of value to explore potential biomarkers for the early identification of sepsis risk and disease monitoring to improve the prognosis in sepsis patients.…”

“…MicroRNAs (MiRNAs) are a class of small non‐coding endogenous molecules RNA (approximately 19‐25 nucleotides in size), which regulate gene expression at post‐transcriptional level by influencing the stability and translation of mRNA . MicroRNA (miR)‐21, a commonly studied miRNA, is shown to regulate inflammation and several organ injuries in the pathogenesis of sepsis . For instance, miR‐21 suppresses lipopolysaccharide (LPS)‐induced inflammation through the toll‐like receptor 4 and nuclear factor kappa‐light‐chain‐enhancer of activated B cells (NF‐κB) pathway in sepsis .…”

“…6 MicroRNA (miR)-21, a commonly studied miRNA, is shown to regulate inflammation and several organ injuries in the pathogenesis of sepsis. [7][8][9] For instance, miR-21 suppresses lipopolysaccharide (LPS)-induced inflammation through the toll-like receptor 4 and nuclear factor kappa-light-chainenhancer of activated B cells (NF-κB) pathway in sepsis. 8 Another study illuminates that upregulation of miR-21 decreases apoptosis and proinflammatory cytokines production in kidneys, hearts, livers, and lungs, implying that miR-21 exerts protective effect on multiple organ failure induced by sepsis.…”