Circulating Soluble ACE2 and Upstream microRNA Expressions in Serum of Type 2 Diabetes Mellitus Patients

The global coronavirus disease 2019 (COVID-19) pandemic was associated with multiple organ failure and comorbidities, such as type 2 diabetes mellitus (T2DM). Risk factors, such as age, gender, and obesity, were associated with COVID-19 infection. Severe acute respiratory syndrome coronavirus 2 (SAR...

Full description

Bibliographic Details
Main Authors: Noha Mousaad Elemam, Hind Hasswan, Hayat Aljaibeji, Nabil Sulaiman
Format: Article
Language:English
Published: MDPI AG 2021-05-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/22/10/5263
_version_ 1797533846922592256
author Noha Mousaad Elemam
Hind Hasswan
Hayat Aljaibeji
Nabil Sulaiman
author_facet Noha Mousaad Elemam
Hind Hasswan
Hayat Aljaibeji
Nabil Sulaiman
author_sort Noha Mousaad Elemam
collection DOAJ
description The global coronavirus disease 2019 (COVID-19) pandemic was associated with multiple organ failure and comorbidities, such as type 2 diabetes mellitus (T2DM). Risk factors, such as age, gender, and obesity, were associated with COVID-19 infection. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is known to use several host receptors for viral entry, such as angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2) in the lung and other organs. However, ACE2 could be shed from the surface to be soluble ACE2 (sACE2) in the circulation. The epigenetic factors affecting ACE2 expression include a type of small non-coding RNAs called microRNAs (miRNAs). In this study, we aimed at exploring the status of the sACE2 as well as serum levels of several upstream novel miRNAs as non-invasive biomarkers that might have a potential role in T2DM patients. Serum samples were collected from 50 T2DM patients and 50 healthy controls, and sACE2 levels were quantified using enzyme-linked immunosorbent assay (ELISA). Also, RNA was extracted, and TaqMan miRNA reverse transcription quantitative PCR (RT-qPCR) was performed to measure serum miRNA levels. Our results revealed that sACE2 is decreased in the T2DM patients and is affected by age, gender, and obesity level. Additionally, 4 miRNAs, which are revealed by in silico analysis to be potentially upstream of ACE2 were detectable in the serum. Among them, miR-421 level was found to be decreased in the serum of diabetic patients, regardless of the presence or absence of diabetic complications, as well as being differential in various body mass index (BMI) groups. The other 3 miRNAs (miR-3909, miR-212-5p, and miR-4677-3p) showed associations with multiple factors including age, gender, BMI, and serum markers, in addition to being correlated to each other. In conclusion, our study reveals a decline in the circulating serum levels of sACE2 in T2DM patients and identified 4 novel miRNAs that were associated with T2DM, which are influenced by different clinical and demographic factors.
first_indexed 2024-03-10T11:21:27Z
format Article
id doaj.art-d875c306c758461bb6b7eb1e3b88cad6
institution Directory Open Access Journal
issn 1661-6596
1422-0067
language English
last_indexed 2024-03-10T11:21:27Z
publishDate 2021-05-01
publisher MDPI AG
record_format Article
series International Journal of Molecular Sciences
spelling doaj.art-d875c306c758461bb6b7eb1e3b88cad62023-11-21T20:03:49ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-05-012210526310.3390/ijms22105263Circulating Soluble ACE2 and Upstream microRNA Expressions in Serum of Type 2 Diabetes Mellitus PatientsNoha Mousaad Elemam0Hind Hasswan1Hayat Aljaibeji2Nabil Sulaiman3Sharjah Institute for Medical Research, College of Medicine, University of Sharjah, Sharjah 27272, United Arab EmiratesSharjah Institute for Medical Research, College of Medicine, University of Sharjah, Sharjah 27272, United Arab EmiratesSharjah Institute for Medical Research, College of Medicine, University of Sharjah, Sharjah 27272, United Arab EmiratesSharjah Institute for Medical Research, College of Medicine, University of Sharjah, Sharjah 27272, United Arab EmiratesThe global coronavirus disease 2019 (COVID-19) pandemic was associated with multiple organ failure and comorbidities, such as type 2 diabetes mellitus (T2DM). Risk factors, such as age, gender, and obesity, were associated with COVID-19 infection. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is known to use several host receptors for viral entry, such as angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2) in the lung and other organs. However, ACE2 could be shed from the surface to be soluble ACE2 (sACE2) in the circulation. The epigenetic factors affecting ACE2 expression include a type of small non-coding RNAs called microRNAs (miRNAs). In this study, we aimed at exploring the status of the sACE2 as well as serum levels of several upstream novel miRNAs as non-invasive biomarkers that might have a potential role in T2DM patients. Serum samples were collected from 50 T2DM patients and 50 healthy controls, and sACE2 levels were quantified using enzyme-linked immunosorbent assay (ELISA). Also, RNA was extracted, and TaqMan miRNA reverse transcription quantitative PCR (RT-qPCR) was performed to measure serum miRNA levels. Our results revealed that sACE2 is decreased in the T2DM patients and is affected by age, gender, and obesity level. Additionally, 4 miRNAs, which are revealed by in silico analysis to be potentially upstream of ACE2 were detectable in the serum. Among them, miR-421 level was found to be decreased in the serum of diabetic patients, regardless of the presence or absence of diabetic complications, as well as being differential in various body mass index (BMI) groups. The other 3 miRNAs (miR-3909, miR-212-5p, and miR-4677-3p) showed associations with multiple factors including age, gender, BMI, and serum markers, in addition to being correlated to each other. In conclusion, our study reveals a decline in the circulating serum levels of sACE2 in T2DM patients and identified 4 novel miRNAs that were associated with T2DM, which are influenced by different clinical and demographic factors.https://www.mdpi.com/1422-0067/22/10/5263miRNAssoluble ACE2type 2 diabetes mellitusbiomarkers
spellingShingle Noha Mousaad Elemam
Hind Hasswan
Hayat Aljaibeji
Nabil Sulaiman
Circulating Soluble ACE2 and Upstream microRNA Expressions in Serum of Type 2 Diabetes Mellitus Patients
International Journal of Molecular Sciences
miRNAs
soluble ACE2
type 2 diabetes mellitus
biomarkers
title Circulating Soluble ACE2 and Upstream microRNA Expressions in Serum of Type 2 Diabetes Mellitus Patients
title_full Circulating Soluble ACE2 and Upstream microRNA Expressions in Serum of Type 2 Diabetes Mellitus Patients
title_fullStr Circulating Soluble ACE2 and Upstream microRNA Expressions in Serum of Type 2 Diabetes Mellitus Patients
title_full_unstemmed Circulating Soluble ACE2 and Upstream microRNA Expressions in Serum of Type 2 Diabetes Mellitus Patients
title_short Circulating Soluble ACE2 and Upstream microRNA Expressions in Serum of Type 2 Diabetes Mellitus Patients
title_sort circulating soluble ace2 and upstream microrna expressions in serum of type 2 diabetes mellitus patients
topic miRNAs
soluble ACE2
type 2 diabetes mellitus
biomarkers
url https://www.mdpi.com/1422-0067/22/10/5263
work_keys_str_mv AT nohamousaadelemam circulatingsolubleace2andupstreammicrornaexpressionsinserumoftype2diabetesmellituspatients
AT hindhasswan circulatingsolubleace2andupstreammicrornaexpressionsinserumoftype2diabetesmellituspatients
AT hayataljaibeji circulatingsolubleace2andupstreammicrornaexpressionsinserumoftype2diabetesmellituspatients
AT nabilsulaiman circulatingsolubleace2andupstreammicrornaexpressionsinserumoftype2diabetesmellituspatients