PMID- 34067683 OWN - NLM STAT- MEDLINE DCOM- 20210614 LR - 20210614 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 22 IP - 10 DP - 2021 May 17 TI - Circulating Soluble ACE2 and Upstream microRNA Expressions in Serum of Type 2 Diabetes Mellitus Patients. LID - 10.3390/ijms22105263 [doi] LID - 5263 AB - 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. FAU - Elemam, Noha Mousaad AU - Elemam NM AUID- ORCID: 0000-0002-3586-6731 AD - Sharjah Institute for Medical Research, College of Medicine, University of Sharjah, Sharjah 27272, United Arab Emirates. FAU - Hasswan, Hind AU - Hasswan H AD - Sharjah Institute for Medical Research, College of Medicine, University of Sharjah, Sharjah 27272, United Arab Emirates. FAU - Aljaibeji, Hayat AU - Aljaibeji H AUID- ORCID: 0000-0002-1716-0743 AD - Sharjah Institute for Medical Research, College of Medicine, University of Sharjah, Sharjah 27272, United Arab Emirates. AD - Department of Neurology, Brigham and Women's Hospital, Boston, MA 02115, USA. FAU - Sulaiman, Nabil AU - Sulaiman N AD - Sharjah Institute for Medical Research, College of Medicine, University of Sharjah, Sharjah 27272, United Arab Emirates. AD - Department of Family Medicine, College of Medicine, University of Sharjah, Sharjah 27272, United Arab Emirates. AD - Baker/IDI Heart and Diabetes Institute, Melbourne, VIC 3004, Australia. LA - eng GR - 120301/National Diabetes and Lifestyle Survey/ PT - Journal Article DEP - 20210517 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (Biomarkers) RN - 0 (MIRN212 microRNA, human) RN - 0 (MIRN421 microRNA, human) RN - 0 (MIRN46773p microRNA, human) RN - 0 (MicroRNAs) RN - EC 3.4.17.23 (Angiotensin-Converting Enzyme 2) SB - IM MH - Adult MH - Angiotensin-Converting Enzyme 2/*blood/genetics/metabolism MH - Biomarkers/blood MH - Body Mass Index MH - COVID-19/blood/complications/genetics MH - Diabetes Complications/*blood/genetics/virology MH - Diabetes Mellitus, Type 2/*blood/genetics/physiopathology/virology MH - Down-Regulation MH - Female MH - Gene Expression Regulation/genetics MH - Humans MH - Male MH - MicroRNAs/*blood/genetics MH - Middle Aged MH - Obesity/blood/genetics PMC - PMC8156444 OTO - NOTNLM OT - biomarkers OT - miRNAs OT - soluble ACE2 OT - type 2 diabetes mellitus COIS- The authors declare no conflict of interest. EDAT- 2021/06/03 06:00 MHDA- 2021/06/16 06:00 PMCR- 2021/05/17 CRDT- 2021/06/02 01:20 PHST- 2021/03/11 00:00 [received] PHST- 2021/05/12 00:00 [revised] PHST- 2021/05/13 00:00 [accepted] PHST- 2021/06/02 01:20 [entrez] PHST- 2021/06/03 06:00 [pubmed] PHST- 2021/06/16 06:00 [medline] PHST- 2021/05/17 00:00 [pmc-release] AID - ijms22105263 [pii] AID - ijms-22-05263 [pii] AID - 10.3390/ijms22105263 [doi] PST - epublish SO - Int J Mol Sci. 2021 May 17;22(10):5263. doi: 10.3390/ijms22105263.