Journal Article

Dysregulated thrombospondin 1 and miRNA-29a-3p in severe COVID-19

Shin, Seul Gi, Silwal, Prashanta, Lee, Sung-Gwon, Kim, Jungok, Sohn, Kyung Mok, Jeong, Hyeongseok, Cheon, Shinhye, Jo, Eun-Kyeong, Kim, Yeon-Sook, Park, Ki-Sun, Kim, In Soo, Kym, Sungmin, Park, Chungoo

2022

Overview

Although nearly a fifth of symptomatic COVID-19 patients suffers from severe pulmonary inflammation, the mechanism of developing severe illness is not yet fully understood. To identify significantly altered genes in severe COVID-19, we generated messenger RNA and micro-RNA profiling data of peripheral blood mononuclear cells (PBMCs) from five COVID-19 patients (2 severe and 3 mild patients) and three healthy controls (HC). For further evaluation, two publicly available RNA-Seq datasets (GSE157103 and GSE152418) and one single-cell RNA-Seq dataset (GSE174072) were employed. Based on RNA-Seq datasets, thrombospondin 1 (THBS1) and interleukin-17 receptor A (IL17RA) were significantly upregulated in severe COVID-19 patients’ blood. From single-cell RNA-sequencing data, IL17RA level is increased in monocytes and neutrophils, whereas THBS1 level is mainly increased in the platelets. Moreover, we identified three differentially expressed microRNAs in severe COVID-19 using micro-RNA sequencings. Intriguingly, hsa-miR-29a-3p significantly downregulated in severe COVID-19 was predicted to bind the 3′-untranslated regions of both IL17RA and THBS1 mRNAs. Further validation analysis of our cohort (8 HC, 7 severe and 8 mild patients) showed that THBS1 , but not IL17RA , was significantly upregulated, whereas hsa-miR-29a-3p was downregulated, in PBMCs from severe patients. These findings strongly suggest that dysregulated expression of THBS1 , IL17RA , and hsa-miR-29a-3p involves severe COVID-19.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 3' Untranslated regions / 631/114/2163 / 631/114/2391 / 692/699/255/2514 / Coronaviruses / COVID-19 / COVID-19 - genetics / Humanities and Social Sciences / Humans / Interleukin 17 / Leukocytes (neutrophilic) / Leukocytes, Mononuclear / MicroRNAs / MicroRNAs - genetics / miRNA / Monocytes / mRNA / multidisciplinary / Peripheral blood mononuclear cells / Science / Science (multidisciplinary) / Thrombospondin / Thrombospondin 1 - genetics