Differentially expressed microRNAs in the corpus cavernosum from a murine model with type 2 diabetes mellitus-associated erectile dysfunction.
To better understand the molecular aetiology of type 2 diabetes mellitus-associated erectile dysfunction (T2DMED) and to provide candidates for further study of its diagnosis and treatment, this study was designed to investigate differentially expressed microRNAs (miRNAs) in the corpus cavernosum (CC) of mice with T2DMED using GeneChip array techniques (Affymetrix miRNA 4.0 Array) and to predict target genes and signalling pathways regulated by these miRNAs based on bioinformatic analysis using TargetScan, the DAIAN web platform and DAVID. In the initial screening, 21 miRNAs appeared distinctly expressed in the T2DMED group (fold change ≥3, p ≤ 0.01). Among them, the differential expression of miR-18a, miR-206, miR-122, and miR-133 were confirmed by qRT-PCR (p < 0.05 and FDR <5 %). According to bioinformatic analysis, the four miRNAs were speculated to play potential roles in the mechanisms of T2DMED via regulating 28 different genes and several pathways, including apoptosis, fibrosis, eNOS/cGMP/PKG, and vascular smooth muscle contraction processes, which mainly focused on influencing the functions of the endothelium and smooth muscle in the CC. IGF-1, as one of the target genes, was verified to decrease in the CCs of T2DMED animals via ELISA and was confirmed as the target of miR-18a or miR-206 via luciferase assay. Finally, these four miRNAs deserve further confirmation as biomarkers of T2DMED in larger studies. Additionally, miR-18a and/or miR-206 may provide new preventive/therapeutic targets for ED management by targeting IGF-1.
State Key Laboratory of Reproductive Medicine, Department of Andrology, Maternity Hospital Affiliated to Nanjing Medical University, Nanjing, China.|State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Jiangsu Engineering Research Center for microRNA Biology and Biotechnology, Nanjing University, Nanjing, China.
Feng
F
Pan
State Key Laboratory of Reproductive Medicine, Department of Andrology, Maternity Hospital Affiliated to Nanjing Medical University, Nanjing, China.|Department of Comparative Medicine, Jinling Hospital, School of Clinical Medicine, Nanjing University, Nanjing, China.
Jinwei
J
You
State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Jiangsu Engineering Research Center for microRNA Biology and Biotechnology, Nanjing University, Nanjing, China.
Yuan
Y
Liu
Department of Andrology, Affiliated Drum Tower Hospital, School of Medicine, Nanjing University, Nanjing, China.
Xuefeng
X
Qiu
Department of Andrology, Affiliated Drum Tower Hospital, School of Medicine, Nanjing University, Nanjing, China.
Wen
W
Yu
State Key Laboratory of Reproductive Medicine, Department of Andrology, Maternity Hospital Affiliated to Nanjing Medical University, Nanjing, China.
Jiehua
J
Ma
State Key Laboratory of Reproductive Medicine, Department of Andrology, Maternity Hospital Affiliated to Nanjing Medical University, Nanjing, China.
Lianjun
L
Pan
State Key Laboratory of Reproductive Medicine, Department of Andrology, Maternity Hospital Affiliated to Nanjing Medical University, Nanjing, China. astrophel27@aliyun.com.
Aixia
A
Zhang
State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Jiangsu Engineering Research Center for microRNA Biology and Biotechnology, Nanjing University, Nanjing, China. qpzhang@nju.edu.cn.
Qipeng
Q
Zhang
D000818:Animals; D019295:Computational Biology / Q000379:methods*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D004195:Disease Models, Animal; D007172:Erectile Dysfunction / Q000235:genetics* / Q000503:physiopathology; D020869:Gene Expression Profiling / Q000379:methods*; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D010413:Penis / Q000378:metabolism / Q000503:physiopathology
D035683:MicroRNAs
Array analysis; Diabetes mellitus; Endothelium; Erectile dysfunction; MicroRNA; Smooth muscle
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