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Long non-coding RNAs in biomarking COVID-19: a machine learning-based approach
Raheleh Heydari1, Mohammad Javad Tavassolifar1, Sara Fayazzadeh2
1Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Insights
Three long non-coding RNAs (lncRNAs) were overexpressed in COVID-19 patients, correlating with inflammation and fibrosis markers. A combination of CRNDE and H19 lncRNAs shows potential as a diagnostic biomarker for COVID-19.
Area of Science:
- Molecular Biology
- Immunology
- Virology
Background:
- The COVID-19 pandemic has caused significant global mortality and morbidity.
- Limited data exists on the role of long non-coding RNAs (lncRNAs) in COVID-19 pathogenesis.
- This study investigates three specific lncRNAs (H19, TUG1, CRNDE) in relation to inflammation and fibrosis in COVID-19 patients.
Purpose of the Study:
- To elucidate the relationship between H19, TUG1, and CRNDE lncRNAs and key inflammatory/fibrotic factors (STAT3, α-SMA, TNF-α, IL-6) in COVID-19 patients.
- To assess the diagnostic potential of these lncRNAs in distinguishing COVID-19 patients from healthy individuals.
Main Methods:
- Collected peripheral blood mononuclear cells from 28 COVID-19 patients and 17 healthy controls.
- Utilized real-time quantitative PCR (RT-qPCR) and Western blotting to measure RNA and protein expression.
- Employed machine learning and ROC curve analysis to evaluate diagnostic capabilities.
Main Results:
- H19, TUG1, and CRNDE were significantly overexpressed in COVID-19 patients compared to controls.
- STAT3 and α-SMA expression increased at transcript and protein levels in patients and correlated with the three lncRNAs.
- IL-6 and TNF-α were also upregulated in COVID-19 patients.
- A CRNDE-H19 panel demonstrated significant ability to distinguish COVID-19 patients (AUC=0.86).
Conclusions:
- Overexpressed lncRNAs in COVID-19 patients may contribute to disease manifestations.
- Co-expression with STAT3 and α-SMA suggests lncRNAs' role in COVID-19-associated inflammation and fibrosis.
- The CRNDE-H19 combination serves as a promising biomarker for COVID-19 screening and diagnosis.
- Further research on lncRNAs could identify new therapeutic targets for viral infections.
Background:
The coronavirus pandemic that started in 2019 has caused the highest mortality and morbidity rates worldwide. Data on the role of long non-coding RNAs (lncRNAs) in coronavirus disease 2019 (COVID-19) is scarce. We aimed to elucidate the relationship of three important lncRNAs in the inflammatory states, H19, taurine upregulated gene 1 (TUG1), and colorectal neoplasia differentially expressed (CRNDE) with key factors in inflammation and fibrosis induction including signal transducer and activator of transcription3 (STAT3), alpha smooth muscle actin (α-SMA), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) in COVID-19 patients with moderate to severe symptoms.
Methods:
Peripheral blood mononuclear cells from 28 COVID-19 patients and 17 healthy controls were collected. The real-time quantitative polymerase chain reaction (RT-qPCR) was performed to evaluate the expression of RNAs and lncRNAs. Western blotting analysis was also performed to determine the expression levels of STAT3 and α-SMA proteins. Machine learning and receiver operating characteristic (ROC) curve analysis were carried out to evaluate the distinguishing ability of lncRNAs.
Results:
The expression levels of H19, TUG1, and CRNDE were significantly overexpressed in COVID-19 patients compared to healthy controls. Moreover, STAT3 and α-SMA expression levels were remarkedly increased at both transcript and protein levels in patients with COVID-19 compared to healthy subjects and were correlated with Three lncRNAs. Likewise, IL-6 and TNF-α were considerably upregulated in COVID-19 patients. Machine learning and ROC curve analysis showed that CRNDE-H19 panel has the proper ability to distinguish COVID-19 patients from healthy individuals (area under the curve (AUC) = 0.86).
Conclusion:
The overexpression of three lncRNAs in COVID-19 patients observed in this study may align with significant manifestations of COVID-19. Furthermore, their co-expression with STAT3 and α-SMA, two critical factors implicated in inflammation and fibrosis induction, underscores their potential involvement in exacerbating cardiovascular, pulmonary and common symptoms and complications associated with COVID-19. The combination of CRNDE and H19 lncRNAs seems to be an impressive host-based biomarker panel for screening and diagnosis of COVID-19 patients from healthy controls. Research into lncRNAs can provide a robust platform to find new viral infection-related mediators and propose novel therapeutic strategies for viral infections and immune disorders.
