Genome-wide differential expression profiling of lncRNAs and mRNAs associated with early diabetic cardiomyopathy

Abstract

Diabetic cardiomyopathy is one of the main causes of heart failure and death in patients with diabetes. There are no effective approaches to preventing its development in the clinic. Long noncoding RNAs (lncRNA) are increasingly recognized as important molecular players in cardiovascular disease. Herein we investigated the profiling of cardiac lncRNA and mRNA expression in type 2 diabetic db/db mice with and without early diabetic cardiomyopathy. We found that db/db mice developed cardiac hypertrophy with normal cardiac function at 6 weeks of age but with a decreased diastolic function at 20 weeks of age. LncRNA and mRNA transcripts were remarkably different in 20-week-old db/db mouse hearts compared with both nondiabetic and diabetic controls. Overall 1479 lncRNA transcripts and 1109 mRNA transcripts were aberrantly expressed in 6- and 20-week-old db/db hearts compared with nondiabetic controls. The lncRNA-mRNA co-expression network analysis revealed that 5 deregulated lncRNAs having maximum connections with differentially expressed mRNAs were BC038927, G730013B05Rik, 2700054A10Rik, AK089884, and Daw1. Bioinformatics analysis revealed that these 5 lncRNAs are closely associated with membrane depolarization, action potential conduction, contraction of cardiac myocytes, and actin filament-based movement of cardiac cells. This study profiles differently expressed lncRNAs in type 2 mice with and without early diabetic cardiomyopathy and identifies BC038927, G730013B05Rik, 2700054A10Rik, AK089884, and Daw1 as the core lncRNA with high significance in diabetic cardiomyopathy.

LncRNA-MIAT-Mediated miR-214-3p Silencing Is Responsible for IL-17 Production and Cardiac Fibrosis in Diabetic Cardiomyopathy

“…LncRNAs are a type of endogenous RNA transcripts longer than 200 nucleotides which epigenetically regulate gene expression but do not have protein-coding potential. To our knowledge, it has found that lncRNAs are aberrantly expressed in DCM, leading to a variety of pathophysiological processes (Pant et al, 2019). LncRNA-MIAT has been first identified to be associated with myocardial infarction in a genome-wide association study in 2006 (Ishii et al, 2006).…”

<p>LncRNA SNHG11 Promotes Proliferation, Migration, Apoptosis, and Autophagy by Regulating hsa-miR-184/AGO2 in HCC</p>

“…LncRNAs have been recognized as being closely related to a variety of diseases, such as the occurrence, development, and prognosis of malignant tumors, cardiovascular diseases, and endocrine diseases, and have played important roles in regulating physiological processes such as cell proliferation, differentiation, and apoptosis. [2][3][4][5][6][7] Therefore, further research and verification of the role of abnormal lncRNA expression in HCC may provide novel ideas for the treatment of HCC.…”

Long noncoding RNA MAPKAPK5-AS1 promotes colorectal cancer progression by cis-regulating the nearby gene MK5 and acting as a let-7f-1-3p sponge

“…Long noncoding RNAs (lncRNAs) are a class of noncoding RNAs with a length greater than 200 nucleotides [ 6 ] and are categorized based on regulating gene expression in cis versus performing functions in trans [ 7 ]. In recent years, emerging evidence has shown that lncRNAs play major roles in the occurrence and development of cardiovascular disease [ 8 ], cardiomyopathy [ 9 ] and mesenchymal stem cells [ 10 , 11 ], in particular, dysregulation of lncRNAs has been discovered in many human cancers [ 12 – 14 ]. For example, HOX transcript antisense RNA (HOTAIR) is the first lncRNA [ 15 ] demonstrated to have a trans -transcriptional regulatory function, and it has been shown to have carcinogenic function in prostate cancer [ 16 ] and breast cancer [ 17 , 18 ].…”