Long noncoding RNA HULC is an independent predictor of COVID-19 severity and mortality in relation to microRNA-9 and IL-6

Marwa M. Esawy; Amir Abd-elhameed; Alshimaa L. Abdallah; Maha E. Alsadik; Elsayed S. Abd elbaser; Marwa A. Shabana; Rania M. Abdullah; Marwa M. Esawy; Amir Abd-elhameed; Alshimaa L. Abdallah; Maha E. Alsadik; Elsayed S. Abd elbaser; Marwa A. Shabana; Rania M. Abdullah

doi:10.3934/molsci.2022005

AIMS Molecular Science

2022, Volume 9, Issue 2: 79-90. doi: 10.3934/molsci.2022005

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Research article

Long noncoding RNA HULC is an independent predictor of COVID-19 severity and mortality in relation to microRNA-9 and IL-6

1.
Clinical Pathology Department, Faculty of Human Medicine, Zagazig University, Egypt
2.
Internal Medicine Department, Faculty of Human Medicine, Zagazig University, Egypt
3.
Microbiology and Immunology Department, Faculty of Human Medicine, Zagazig University, Egypt
4.
Chest Department, Faculty of Human Medicine, Zagazig University, Egypt
5.
Tropical Medicine Department, Faculty of Human Medicine, Zagazig University, Egypt

Received: 16 March 2022 Revised: 27 May 2022 Accepted: 08 June 2022 Published: 16 June 2022

LncRNA HULC regulates inflammation in vascular endothelial cells resulting in their dysfunction. Endothelial dysfunction contributes to severe COVID-19. lncRNA HULC targets miRNA-9 that play roles in the pathogenesis and progression of COVID-19 through the acute inflammatory response mediated by IL-6. This study aimed to evaluate the role of lncRNA HULC, miRNA-9, and IL-6 in estimating the severity and predicting the prognosis of COVID-19. There were 38 non-severe, 38 severe COVID-19 patients, and 38 healthy controls enrolled in this study. Expression of lncRNA HULC and miRNA-9 was performed using RT-qPCR. ELISA was utilized to measure serum IL-6. Expression of lncRNA HULC and IL-6 level were increased in severe patients compared to non-severe patients and controls (p < 0.001). MiRNA-9 showed the lowest expression levels in the severe patients in comparison with non-severe patients and controls (p < 0.001) lncRNA HULC was negatively correlated with miRNA-9 (p < 0.001, r = −0.582) and positively correlated with IL-6 (p < 0.001, r = 0.567). Furthermore, miRNA-9 showed a negative correlation with IL-6 (p < 0.001, r = −0.0466). For severity prediction, lncRNA HULC expression had an adjusted OR of 52.5 (95% CI: 1.43−192.2, p = 0.031). The lncRNA HULC had an adjusted mortality hazard ratio of 1.9 (95% CI: 1.02−3.56, p = 0.043) after the adjustment of IL-6. So, in COVID-19 patients, the lncRNA HULC had a positive correlation with IL-6 and a negative correlation with miRNA-9. The COVID-19 severity and mortality appear to be predicted independently by the lncRNA HULC.
- COVID-19,
- Interleukin-6,
- lncRNA HULC,
- miRNA-9,
- mortality,
- severity
Citation: Marwa M. Esawy, Amir Abd-elhameed, Alshimaa L. Abdallah, Maha E. Alsadik, Elsayed S. Abd elbaser, Marwa A. Shabana, Rania M. Abdullah. Long noncoding RNA HULC is an independent predictor of COVID-19 severity and mortality in relation to microRNA-9 and IL-6[J]. AIMS Molecular Science, 2022, 9(2): 79-90. doi: 10.3934/molsci.2022005

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Abstract

LncRNA HULC regulates inflammation in vascular endothelial cells resulting in their dysfunction. Endothelial dysfunction contributes to severe COVID-19. lncRNA HULC targets miRNA-9 that play roles in the pathogenesis and progression of COVID-19 through the acute inflammatory response mediated by IL-6. This study aimed to evaluate the role of lncRNA HULC, miRNA-9, and IL-6 in estimating the severity and predicting the prognosis of COVID-19. There were 38 non-severe, 38 severe COVID-19 patients, and 38 healthy controls enrolled in this study. Expression of lncRNA HULC and miRNA-9 was performed using RT-qPCR. ELISA was utilized to measure serum IL-6. Expression of lncRNA HULC and IL-6 level were increased in severe patients compared to non-severe patients and controls (p < 0.001). MiRNA-9 showed the lowest expression levels in the severe patients in comparison with non-severe patients and controls (p < 0.001) lncRNA HULC was negatively correlated with miRNA-9 (p < 0.001, r = −0.582) and positively correlated with IL-6 (p < 0.001, r = 0.567). Furthermore, miRNA-9 showed a negative correlation with IL-6 (p < 0.001, r = −0.0466). For severity prediction, lncRNA HULC expression had an adjusted OR of 52.5 (95% CI: 1.43−192.2, p = 0.031). The lncRNA HULC had an adjusted mortality hazard ratio of 1.9 (95% CI: 1.02−3.56, p = 0.043) after the adjustment of IL-6. So, in COVID-19 patients, the lncRNA HULC had a positive correlation with IL-6 and a negative correlation with miRNA-9. The COVID-19 severity and mortality appear to be predicted independently by the lncRNA HULC.

Abbreviations

AUC

area under the ROC curve

Confidence interval

COVID-19

Coronavirus disease 2019

HULC

Highly upregulated in liver cancer

IL-6

Interleukin-6

lncRNA

Long noncoding RNA (lncRNA)

MicroRNA

miRNA

ROC

Receiver Operator Characteristic

Reverse transcription

RT-qPCR

Quantitative real-time polymerase chain reaction

Conflict of interest

All authors declare no conflicts of interest in this paper.

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