Long Non-Coding RNAs ANRIL and HOTAIR Upregulation is Associated with Survival in Neonates with Sepsis in a Neonatal Intensive Care Unit

Abstract

BackgroundRecently, long non-coding RNAs (lncRNAs) have emerged as potential molecular biomarkers for sepsis. We aimed to profile the expression signature of three inflammation-related lncRNAs, MALAT1, ANRIL, and HHOTAIR, in the plasma of neonates with sepsis and correlate these signatures with the phenotype.Patients and MethodsThis case–control study included 124 neonates with sepsis (88 survivors/36 non-survivors) admitted to the neonatal ICU and 17 healthy neonates. The relative expressions were quantified by real-time PCR and correlated to the clinic-laboratory data.ResultsThe three circulating lncRNAs were upregulated in the cases; the median levels were MALAT1 (median = 1.71, IQR: −0.5 to 3.27), ANRIL (median = 1.09, IQR: 0.89 to 1.30), and HOTAIR (median = 1.83, IQR: 1.44 to 2.41). Co-expression analysis showed that the three studied lncRNAs were directly correlated (all p-values <0.001). Overall and stratification by sex analyses revealed significantly higher levels of the three lncRNAs in non-survivors compared to the survivor group (all p-values <0.001). Principal component analysis showed a clear demarcation between the two study cohorts in males and females. Cohorts with upregulated ANRIL (hazard ratio; HR = 4.21, 95% CI = 1.15–10.4, p=0.030) and HOTAIR (HR = 2.49, 95% CI = 1.02–6.05, p=0.044) were at a higher risk of mortality.ConclusionCirculatory MALAT1, ANRIL, and HOTAIR were upregulated in neonatal sepsis, and the latter two may have the potential as prognostic biomarkers for survival in neonatal sepsis.