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

Abstract

Nouran B AbdAllah,1 Essam Al Ageeli,2 Abdullah Shbeer,3 Jawaher A Abdulhakim,4 Eman A Toraih,5,6 Doaa O Salman,6 Manal S Fawzy,7,8 Sanaa S Nassar1 1Department of Pediatrics, Faculty of Medicine, Suez Canal University, Ismailia, Egypt; 2Department of Clinical Biochemistry (Medical Genetics), Faculty of Medicine, Jazan University, Jazan, Saudi Arabia; 3Anesthesiology and Intensive Care, Department of Surgery, Faculty of Medicine, Jazan University, Jazan, Saudi Arabia; 4Medical Laboratory Department, College of Applied Medical Sciences, Taibah University, Yanbu, Saudi Arabia; 5Division of Endocrine and Oncologic Surgery, Department of Surgery, School of Medicine, Tulane University, New Orleans, LA, USA; 6Genetics Unit, Department of Histology and Cell Biology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt; 7Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt; 8Department of Biochemistry, Faculty of Medicine, Northern Border University, Arar, Saudi ArabiaCorrespondence: Manal S Fawzy, Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt, Email [email protected] Eman A Toraih, Division of Endocrine and Oncologic Surgery, Department of Surgery, School of Medicine, Tulane University, New Orleans, LA, USA, Email [email protected]: Recently, 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 Methods: This 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.Results: The 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.Conclusion: Circulatory 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.Keywords: neonatal sepsis, long non-coding RNAs, MALAT1, ANRIL, HOTAIR, survival

Keywords

• neonatal sepsis
• long non-coding rnas
• malat1
• anril
• hotair
• survival