Identification of Circulating miR-101, miR-375 and miR-802 as Biomarkers for Type 2 Diabetes

被引:177
作者
Higuchi, Chigusa [1 ]
Nakatsuka, Atsuko [1 ]
Eguchi, Jun [1 ]
Teshigawara, Sanae [1 ]
Kanzaki, Motoko [1 ]
Katayama, Akihiro [1 ]
Yamaguchi, Satoshi [1 ]
Takahashi, Naoto [1 ]
Murakami, Kazutoshi [1 ,2 ]
Ogawa, Daisuke [3 ]
Sasaki, Sakiko [4 ]
Makino, Hirofumi [1 ]
Wada, Jun [1 ]
机构
[1] Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Med & Clin Sci, Kita Ku, Okayama 7008558, Japan
[2] Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Gen Med, Kita Ku, Okayama 7008558, Japan
[3] Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Diabet Nephropathy, Kita Ku, Okayama 7008558, Japan
[4] Okayama Southern Inst Hlth, Kita Ku, Okayama, Japan
来源
METABOLISM-CLINICAL AND EXPERIMENTAL | 2015年 / 64卷 / 04期
关键词
miRNA; Liver; Adipose tissues; Serum; Diabetes; MICRORNAS; OVEREXPRESSION; EXPRESSION; CANCER;
D O I
10.1016/j.metabol.2014.12.003
中图分类号
R5 [内科学];
学科分类号
100201 [内科学];
摘要
Purpose. The unique circulating microRNAs (miRNAs) observed in patients with type 2 diabetes (T2D) are candidates as new biomarkers and therapeutic targets. In order to identify circulating miRNAs relevant to the disease process in case of type 2 diabetes, we performed the Illumina sequencing of miRNAs derived from the serum, liver and epididymal white adipose tissue (WAT) of diet-induced obese male C57BL/6J mice. Basic Procedures. We selected four miRNAs, miR-101, miR-335, miR-375, and miR-802, which are increased in the sera and tissues of obese mice, and measured the serum levels of miRNAs in T2D and subjects with normal glucose tolerance (NGT). Main Findings. The serum concentrations of miRNAs, log10miR-101, log(10)miR-375, and log(10)miR-802, were significantly increased in the T2D patients compared with NGT subjects (1.41 +/- 2.01 u.s. -0.57 +/- 1.05 (P = 1.36 x 10(-5)), 0.20 +/- 0.58 v.s. 0.038 +/- 1.00 (P = 3.06 x 10(-6)), and 2.45 +/- 1.27 u.s. 0.97 +/- 0.98 (P = 0.014), respectively). The log(10)miR-335 values did not demonstrate any significant differences between the T2D and NGT groups (-1.08 +/- 1.35 v.s. 0.38 +/- 1.21 (P = 0.25)). According to the stepwise regression analysis, the HbA1c was an independent predictor of miR-101. Regarding the serum miR-802 levels, eGFR, HbA1c and HDL-C values were identified as significant determinants. Principal Conclusions. The present findings demonstrated that the circulating miR-101, miR-375 and miR-802 levels are significantly increased in T2D patients versus NGT subjects and they may become the new biomarkers for type 2 diabetes. (C) 2015 Elsevier Inc. All rights reserved.
引用
收藏
页码:489 / 497
页数:9
相关论文
共 29 条
[1]
Intercellular Transport of MicroRNAs [J].
Boon, Reinier A. ;
Vickers, Kasey C. .
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 2013, 33 (02) :186-192
[2]
miRNAs in Insulin Resistance and Diabetes-Associated Pancreatic Cancer: The 'Minute and Miracle' Molecule Moving as a Monitor in the 'Genomic Galaxy' [J].
Chakraborty, Chiranjib ;
Doss, George Priya C. ;
Bandyopadhyay, Sanghamitra .
CURRENT DRUG TARGETS, 2013, 14 (10) :1110-1117
[3]
Differential Glucose-Regulation of MicroRNAs in Pancreatic Islets of Non-Obese Type 2 Diabetes Model Goto-Kakizaki Rat [J].
Esguerra, Jonathan Lou S. ;
Bolmeson, Caroline ;
Cilio, Corrado M. ;
Eliasson, Lena .
PLOS ONE, 2011, 6 (04)
[4]
Circulating microRNAs as novel biomarkers for diabetes mellitus [J].
Guay, Claudiane ;
Regazzi, Romano .
NATURE REVIEWS ENDOCRINOLOGY, 2013, 9 (09) :513-521
[5]
Expression of islet-specific microRNAs during human pancreatic development [J].
Joglekar, Mugdha V. ;
Joglekar, Vinay M. ;
Hardikar, Anandwardhan A. .
GENE EXPRESSION PATTERNS, 2009, 9 (02) :109-113
[6]
Targeting the Circulating MicroRNA Signature of Obesity [J].
Jose Ortega, Francisco ;
Maria Mercader, Josep ;
Catalan, Victoria ;
Maria Moreno-Navarrete, Jose ;
Pueyo, Neus ;
Sabater, Monica ;
Gomez-Ambrosi, Javier ;
Anglada, Roger ;
Antonio Fernandez-Formoso, Jose ;
Ricart, Wifredo ;
Fruehbeck, Gema ;
Manuel Fernandez-Real, Jose .
CLINICAL CHEMISTRY, 2013, 59 (05) :781-792
[7]
Circulating miRNA Profiles in Patients with Metabolic Syndrome [J].
Karolina, Dwi Setyowati ;
Tavintharan, Subramaniam ;
Armugam, Arunmozhiarasi ;
Sepramaniam, Sugunavathi ;
Pek, Sharon Li Ting ;
Wong, Michael T. K. ;
Lim, Su Chi ;
Sum, Chee Fang ;
Jeyaseelan, Kandiah .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2012, 97 (12) :E2271-E2276
[8]
Biogenesis of small RNAs in animals [J].
Kim, V. Narry ;
Han, Jinju ;
Siomi, Mikiko C. .
NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2009, 10 (02) :126-139
[9]
Obesity-induced overexpression of miR-802 impairs glucose metabolism through silencing of Hnf1b [J].
Kornfeld, Jan-Wilhelm ;
Baitzel, Catherina ;
Koenner, A. Christine ;
Nicholls, Hayley T. ;
Vogt, Merly C. ;
Herrmanns, Karolin ;
Scheja, Ludger ;
Haumaitre, Cecile ;
Wolf, Anna M. ;
Knippschild, Uwe ;
Seibler, Jost ;
Cereghini, Silvia ;
Heeren, Joerg ;
Stoffel, Markus ;
Bruening, Jens C. .
NATURE, 2013, 494 (7435) :111-115
[10]
Lahmy R, 2014, MOL BIOL REP