PMID- 34262334 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220424 IS - 1178-7074 (Print) IS - 1178-7074 (Electronic) IS - 1178-7074 (Linking) VI - 14 DP - 2021 TI - Identification of an miRNA Regulatory Network and Candidate Markers for Ischemic Stroke Related to Diabetes. PG - 3213-3223 LID - 10.2147/IJGM.S319503 [doi] AB - PURPOSE: Type 2 diabetes mellitus (T2DM) increases the risk of ischemic stroke and poor prognosis. This study aimed to identify molecular mechanisms that are dysregulated in T2DM-associated ischemic stroke and candidate genes that might serve as biomarkers. METHODS: The top 25% variance genes in the GSE21321 and GSE22255 datasets were analyzed for coexpression. The differentially expressed mRNAs (DEmRs) between patients with T2DM or ischemic stroke and controls were analyzed. Then, the union of overlapping coexpressed genes and overlapping DEmRs was analyzed. The miRNAs differentially expressed in T2DM-associated ischemic stroke were also analyzed. CIBERSORT was used to evaluate the levels of infiltration by immune cells in T2DM-associated stroke. RESULTS: Thirteen coexpression modules were identified in T2DM and 10 in ischemic stroke, and 594 module genes were shared between the two conditions. A total of 4452 mRNAs differentially expressed between T2DM patients and controls were identified, as were 2390 mRNAs differentially expressed between ischemic stroke and controls. The 771 union genes were enriched mainly in immune-related biological functions and signaling pathways. UBE2N, TGFB3, EXOSC1, and VIM were identified as candidate markers. In addition, we identified miR-576-3p as having the most regulatory roles in both T2DM and ischemic stroke. Mast cell activation was significantly down-regulated in T2DM but up-regulated in ischemic stroke. CONCLUSION: These findings provide numerous testable hypotheses about the pathways underlying T2DM-associated ischemic stroke, which may help identify therapeutic targets. CI - (c) 2021 Zhou et al. FAU - Zhou, Hui AU - Zhou H AD - Department of Neurology, The People's Hospital of Guiping, Guiping, Guangxi, 537200, People's Republic of China. FAU - Huang, Liujia AU - Huang L AD - Department of Rehabilitation Medicine, The People's Hospital of Guiping, Guiping, Guangxi, 537200, People's Republic of China. FAU - Liang, Lucong AU - Liang L AD - Department of Neurology, The Fifth Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530022, People's Republic of China. FAU - Chen, Liechun AU - Chen L AD - Department of Neurology, The Fifth Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530022, People's Republic of China. FAU - Zou, Chun AU - Zou C AD - Department of Neurology, The Fifth Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530022, People's Republic of China. FAU - Li, Zhenhua AU - Li Z AD - Department of Emergency Medicine, The First People's Hospital of Nanning, Nanning, 530022, People's Republic of China. FAU - Li, Rongjie AU - Li R AD - Department of Neurology, The Fifth Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530022, People's Republic of China. FAU - Jian, Chongdong AU - Jian C AD - Department of Neurology, The Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi, 533000, People's Republic of China. FAU - Zou, Donghua AU - Zou D AUID- ORCID: 0000-0002-3891-9472 AD - Department of Neurology, The Fifth Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530022, People's Republic of China. LA - eng PT - Journal Article DEP - 20210707 PL - New Zealand TA - Int J Gen Med JT - International journal of general medicine JID - 101515487 PMC - PMC8274709 OTO - NOTNLM OT - candidate gene OT - immune response OT - ischemic stroke OT - miRNAs OT - type 2 diabetes mellitus COIS- The authors declare that this research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2021/07/16 06:00 MHDA- 2021/07/16 06:01 PMCR- 2021/07/07 CRDT- 2021/07/15 06:17 PHST- 2021/05/12 00:00 [received] PHST- 2021/06/29 00:00 [accepted] PHST- 2021/07/15 06:17 [entrez] PHST- 2021/07/16 06:00 [pubmed] PHST- 2021/07/16 06:01 [medline] PHST- 2021/07/07 00:00 [pmc-release] AID - 319503 [pii] AID - 10.2147/IJGM.S319503 [doi] PST - epublish SO - Int J Gen Med. 2021 Jul 7;14:3213-3223. doi: 10.2147/IJGM.S319503. eCollection 2021.