PMID- 37223012 OWN - NLM STAT- MEDLINE DCOM- 20230526 LR - 20231101 IS - 1664-2392 (Print) IS - 1664-2392 (Electronic) IS - 1664-2392 (Linking) VI - 14 DP - 2023 TI - Analysis of mRNA-miRNA-lncRNA differential expression in prediabetes/type 2 diabetes mellitus patients as potential players in insulin resistance. PG - 1131171 LID - 10.3389/fendo.2023.1131171 [doi] LID - 1131171 AB - INTRODUCTION: Type 2 diabetes mellitus (T2DM) is a major global health concern. It usually develops gradually and is frequently preceded by undetectable pre-diabetes mellitus (pre-DM) stage. The purpose of this study was to identify a novel set of seven candidate genes associated with the pathogenesis of insulin resistance (IR) and pre-DM, followed by their experimental validation in patients' serum samples. METHODS: We used the bioinformatics tools and through a two-step process, we first identified and verified two mRNA candidate genes linked to insulin resistance molecular pathogenesis. Second, we identified a non-coding RNAs related to the selected mRNAs and implicated in the insulin resistance molecular pathways followed by pilot study for the RNA panel differential expression in 66 patients with T2DM, 49 individuals with prediabetes and 45 matched controls using real time PCR. RESULTS: The levels of expression of TMEM173 and CHUK mRNAs, hsa-miR (-611, -5192, and -1976) miRNAs gradually increased from the healthy control group to the prediabetic group, reaching their maximum levels in the T2DM group (p <10-3), whereas the levels of expression of RP4-605O3.4 and AC074117.2 lncRNAs declined gradually from the healthy control group to the prediabetic group, reaching their lowest levels in the T2DM group (p <10-3). TMEM173, CHUK mRNAs, hsa_miR (-611 & -1976) and RP4-605O3.4 lncRNA were useful in distinguishing insulin resistant from insulin sensitive groups. miR_611 together with RP4-605O3.4 exhibited significant difference in good versus poor glycemic control groups. DISCUSSION: The presented study provides an insight about this RNA based STING/NOD/IR associated panel that could be used for PreDM-T2DM diagnosis and also as a therapeutic target based on the differences of its expression level in the pre-DM and T2DM stages. CI - Copyright (c) 2023 Ali, Kamel, Agwa, Hakeem, Meteini and Matboli. FAU - Ali, Hebatalla Said AU - Ali HS AD - Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Ain Shams University, Abbassia, Cairo, Egypt. FAU - Kamel, Marwa Mostafa AU - Kamel MM AD - Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Ain Shams University, Abbassia, Cairo, Egypt. FAU - Agwa, Sara H A AU - Agwa SHA AD - Clinical Pathology, Medical Ain Shams Research Institute, Ain Shams University, Cairo, Egypt. FAU - Hakeem, Mohamed S Abdel AU - Hakeem MSA AD - Institute of Immunology, University of Pennsylvania, Philadelphia, PA, United States. FAU - Meteini, Mahmoud Shawky El AU - Meteini MSE AD - Department of General Surgery, The School of Medicine, University of Ain Shams, Cairo, Egypt. FAU - Matboli, Marwa AU - Matboli M AD - Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Ain Shams University, Abbassia, Cairo, Egypt. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20230508 PL - Switzerland TA - Front Endocrinol (Lausanne) JT - Frontiers in endocrinology JID - 101555782 RN - 0 (MicroRNAs) RN - 0 (RNA, Long Noncoding) RN - 0 (Insulin) RN - 0 (RNA, Messenger) SB - IM MH - Humans MH - *MicroRNAs/genetics MH - *Prediabetic State/genetics MH - *Diabetes Mellitus, Type 2/genetics MH - *RNA, Long Noncoding/genetics MH - *Insulin Resistance/genetics MH - Pilot Projects MH - Insulin MH - RNA, Messenger/genetics PMC - PMC10200895 OTO - NOTNLM OT - bioinformatics OT - biomarkers OT - insulin resistance OT - non-coding RNA OT - pre-diabetes OT - type 2 diabetes mellitus COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2023/05/24 13:08 MHDA- 2023/05/26 06:42 PMCR- 2023/01/01 CRDT- 2023/05/24 11:40 PHST- 2022/12/24 00:00 [received] PHST- 2023/04/10 00:00 [accepted] PHST- 2023/05/26 06:42 [medline] PHST- 2023/05/24 13:08 [pubmed] PHST- 2023/05/24 11:40 [entrez] PHST- 2023/01/01 00:00 [pmc-release] AID - 10.3389/fendo.2023.1131171 [doi] PST - epublish SO - Front Endocrinol (Lausanne). 2023 May 8;14:1131171. doi: 10.3389/fendo.2023.1131171. eCollection 2023.