Investigating microRNAs in diabetic cardiomyopathy as tools for early detection and therapeutics

Abstract

To profile microRNAs population of glucose-induced cardiomyoblast cell line and identify the differentially expressed microRNAs and their role under pre-diabetes and diabetes condition in vitro. Rat fetal ventricular cardiomyoblast cell line H9c2 was treated with d-glucose to mimic pre-diabetic, diabetic, and high-glucose conditions. Alteration in cellular, nuclear morphology, and change in ROS generation was analyzed through fluorescent staining. Small RNA sequencing was performed using Illumina NextSeq 550 sequencer and was validated using stem-loop qRT-PCR. A large number (~ 100) differential miRNAs were detected in each treated samples as compared to control; however, a similar expression pattern was observed between pre-diabetes and diabetes conditions with the exception for miR-429, miR-101b-5p, miR-503-3p, miR-384-5p, miR-412-5p, miR-672-5p, and miR-532-3p. Functional annotation of differential expressed target genes revealed their involvement in significantly enriched key pathways associated with diabetic cardiomyopathy. For the first time, we report the differential expression of miRNAs (miR-1249, miR-3596d, miR-3586-3p, miR-7b-3p, miR-191, miR-330-3p, miR-328a, let7i-5p, miR-146-3p, miR-26a-3p) in diabetes-induced cardiac cells. Hyperglycemia threatens the cell homeostasis by dysregulation of miRNAs that begins at a glucose level 10 mM and remains undetected. Analysis of differential expressed miRNAs in prediabetes and diabetes conditions and their role in regulatory mechanisms of diabetic cardiomyopathy holds high potential in the direction of using miRNAs as minimally invasive diagnostic and therapeutic tools.

MiR-503-5p alleviates peripheral neuropathy-induced neuropathic pain in T2DM mice by regulating SEPT9 to inhibit astrocyte activation

“…There are many studies on the role of miR-503-5p in different cancers, but few studies have examined its role in DM and its related complications. In diabetic cardiomyopathy and foot syndrome, the expression of miR-503-5p is significantly upregulated 14 , 15 . Contrary to previous studies, this project shows that miR-503-5p expression is down regulated in DPN.…”

“…miR-503-5p also plays an important role in the development of diabetic complications. In diabetic cardiomyopathy and foot syndrome, the expression of miR-503-5p is significantly upregulated 14 , 15 . In diabetic nephropathy, miR-503-5p enhances endoplasmic reticulum stress and cell apoptosis by downregulating BCL-2 16 .…”

Mitochondrial transplantation: opportunities and challenges in the treatment of obesity, diabetes, and nonalcoholic fatty liver disease

“…It is also associated with mitochondrial dysfunction [58]. In addition, mitochondrial dysfunction contributes greatly to age-dependent IR [59] and induces diabetic microvascular (cardiomyopathy, nephropathy, retinopathy, and neuropathy) [60][61][62][63] and macrovascular (myocardial ischemia) [64] complications. Therefore, mitochondrial quality control is a promising intervention for managing T2D and obesity.…”

MALAT1/miR‐185‐5p mediated high glucose‐induced oxidative stress, mitochondrial injury and cardiomyocyte apoptosis via the RhoA/ROCK pathway

“…MiRNAs are composed of approximately 22 nucleotide sequence, and regulate the expression of target genes at the post‐transcriptional levels via binding to the untranslated regions (UTRs) of complementary message RNAs 13 . Several studies have verified that the differential expression of miRNAs in myocardium are involved in DCM in either patients or animal models with DM 14–17 . Recently, we screened the expression profiles of miRNAs in myocardium from DCM mice, and found that miR‐185‐5p, one of the differentially expressed miRNAs, was markedly down‐regulated in DCM mice (Figure 2A).…”

“… 13 Several studies have verified that the differential expression of miRNAs in myocardium are involved in DCM in either patients or animal models with DM. 14 , 15 , 16 , 17 Recently, we screened the expression profiles of miRNAs in myocardium from DCM mice, and found that miR‐185‐5p, one of the differentially expressed miRNAs, was markedly down‐regulated in DCM mice (Figure 2A ). The miRNA candidate target mRNAs were predicted by miRDB database ( http://mirdb.org/miRDB/ ), and RhoA was shown to be a target gene of miR‐185‐5p, which were verified by NCBI ( http://www.ncbi.nlm.nih.gov/ ).…”