From Euglycemia to Recent Onset of Type 2 Diabetes Mellitus: A Proof-of-Concept Study on Circulating microRNA Profiling Reveals Distinct, and Early microRNA Signatures

被引:7
作者
Greco, Marta [1 ]
Mirabelli, Maria [1 ]
Salatino, Alessandro [1 ]
Accattato, Francesca [1 ]
Aiello, Vincenzo [2 ]
Brunetti, Francesco S. [1 ]
Chiefari, Eusebio [1 ]
Pullano, Salvatore A. [1 ]
Fiorillo, Antonino S. [1 ]
Foti, Daniela P. [3 ]
Brunetti, Antonio [1 ]
机构
[1] Magna Graecia Univ Catanzaro, Dept Hlth Sci, I-88100 Catanzaro, Italy
[2] Vanvitelli Univ, Dept Precis Med, I-80133 Naples, Italy
[3] Magna Graecia Univ Catanzaro, Dept Expt & Clin Med, I-88100 Catanzaro, Italy
关键词
type; 2; diabetes; impaired fasting glucose; circulating miRNAs; biomarkers; NF-KAPPA-B; GENE; IDENTIFICATION; EXPRESSION; BIOMARKERS; VARIANTS; GLUCOSE; MARKERS;
D O I
10.3390/diagnostics13142443
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background and aim-Alterations in circulating microRNA (miRNA) expression patterns are thought to be involved in the early stages of prediabetes, as well as in the progression to overt type 2 diabetes mellitus (T2D) and its vascular complications. However, most research findings are conflicting, in part due to differences in miRNA extraction and normalization methods, and in part due to differences in the study populations and their selection. This cross-sectional study seeks to find new potentially useful biomarkers to predict and/or diagnose T2D by investigating the differential expression patterns of circulating miRNAs in the serum of patients with impaired fasting glucose (IFG) and new-onset T2D, with respect to euglycemic controls, using a high-throughput 384-well array and real-time PCR. Methods-Thirty subjects, aged 45-65 years, classified into three matched groups (of 10 participants each) according to their glycometabolic status, namely (1) healthy euglycemic controls, (2) patients with IFG and (3) patients with new-onset, uncomplicated T2D (<2 years since diagnosis) were enrolled. Circulating miRNAs were extracted from blood serum and profiled through real-time PCR on a commercial 384 well-array, containing spotted forward primers for 372 miRNAs. Data analysis was performed by using the online data analysis software GeneGlobe and normalized by the global Ct mean method. Results-Of the 372 analyzed miRNAs, 33 showed a considerably different expression in IFG and new-onset T2D compared to healthy euglycemic controls, with 2 of them down-regulated and 31 up-regulated. Stringent analysis conditions, using a differential fold regulation threshold & GE; 10, revealed that nine miRNAs (hsa-miR-3610, hsa-miR-3200-5p, hsa-miR-4651, hsa-miR-3135b, hsa-miR-1281, hsa-miR-4301, hsa-miR-195-5p, hsa-miR-523-5p and hsa-let-7a-5p) showed a specific increase in new-onset T2D patients compared to IFG patients, suggesting their possible role as early biomarkers of progression from prediabetes to T2D. Moreover, by conventional fold regulation thresholds of & PLUSMN;2, hsa-miR-146a-5p was down-regulated and miR-1225-3p up-regulated in new-onset T2D patients only. Whereas hsa-miR-146a-5p has a well-known role in glucose metabolism, insulin resistance and T2D complications, no association between hsa-miR-1225-3p and T2D has been previously reported. Bioinformatic and computational analysis predict a role of hsa-miR-1225-3p in the pathogenesis of T2D through the interaction with MAP3K1 and HMGA1. Conclusions-The outcomes of this study could aid in the identification and characterization of circulating miRNAs as potential novel biomarkers for the early diagnosis of T2D and may serve as a proof-of-concept for future mechanistic investigations.
引用
收藏
页数:17
相关论文
共 63 条
[1]  
Alipoor B, 2017, INT J MOL CELL MED, V6, P156, DOI 10.22088/acadpub.BUMS.6.3.156
[2]   2. Classification and Diagnosis of Diabetes: Standards of Medical Care in Diabetes-2022 [J].
American Diabetes Association Professional Practice Committee .
DIABETES CARE, 2022, 45 :S17-S38
[3]   Obesity-related hypoxia via miR-128 decreases insulin-receptor expression in human and mouse adipose tissue promoting systemic insulin resistance [J].
Arcidiacono, Biagio ;
Chiefari, Eusebio ;
Foryst-Ludwig, Anna ;
Curro, Giuseppe ;
Navarra, Giuseppe ;
Brunetti, Francesco S. ;
Mirabelli, Maria ;
Corigliano, Domenica M. ;
Kintscher, Ulrich ;
Britti, Domenico ;
Mollace, Vincenzo ;
Foti, Daniela P. ;
Goldfine, Ira D. ;
Brunetti, Antonio .
EBIOMEDICINE, 2020, 59
[4]   MicroRNAs: Genomics, biogenesis, mechanism, and function (Reprinted from Cell, vol 116, pg 281-297, 2004) [J].
Bartel, David P. .
CELL, 2007, 131 (04) :11-29
[5]   Glucose Regulates Free Cytosolic Zn2+ Concentration, Slc39 (ZiP), and Metallothionein Gene Expression in Primary Pancreatic Islet β-Cells [J].
Bellomo, Elisa A. ;
Meur, Gargi ;
Rutter, Guy A. .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2011, 286 (29) :25778-25789
[6]   A small circulating miRNAs signature predicts mortality and adverse cardiovascular outcomes in chronic hemodialysis patients [J].
Bolignano, Davide ;
Greco, Marta ;
Presta, Pierangela ;
Duni, Anila ;
Vita, Caterina ;
Pappas, Ethymios ;
Mirabelli, Maria ;
Lakkas, Lampros ;
Naka, Katerina K. ;
Brunetti, Antonio ;
Foti, Daniela Patrizia ;
Andreucci, Michele ;
Coppolino, Giuseppe ;
Dounousi, Evangelia .
CLINICAL KIDNEY JOURNAL, 2023, 16 (05) :868-878
[7]   Prediabetes as a toxic environment for the initiation of microvascular and macrovascular complications [J].
Brannick, Ben ;
Wynn, Anne ;
Dagogo-Jack, Samuel .
EXPERIMENTAL BIOLOGY AND MEDICINE, 2016, 241 (12) :1323-1331
[8]   Human diabetes associated with defects in nuclear regulatory proteins for the insulin receptor gene [J].
Brunetti, A ;
Brunetti, L ;
Foti, D ;
Accili, D ;
Goldfine, ID .
JOURNAL OF CLINICAL INVESTIGATION, 1996, 97 (01) :258-262
[9]   The Association of Soluble IGF2R and IGF2R Gene Polymorphism with Type 2 Diabetes [J].
Chanprasertyothin, Suwannee ;
Jongjaroenprasert, Wallaya ;
Ongphiphadhanakul, Boonsong .
JOURNAL OF DIABETES RESEARCH, 2015, 2015
[10]   Comparison of Data Normalization Strategies for Array-Based MicroRNA Profiling Experiments and Identification and Validation of Circulating MicroRNAs as Endogenous Controls in Hypertension [J].
Chekka, Lakshmi Manasa S. ;
Langaee, Taimour ;
Johnson, Julie A. .
FRONTIERS IN GENETICS, 2022, 13