miR-21: a non‐specific biomarker of all maladies

Jenike, Ana E; Halushka, Marc K.

doi:10.1186/s40364-021-00272-1

Cited by 153 publications

(121 citation statements)

References 80 publications

(42 reference statements)

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“…Furthermore, fat tissue-related specific alterations in the expression pattern of miRNAs related to inflammatory processes (15) have also been demonstrated (16,17). miRNA-21 is one of the most abundant and highly conserved recognized miRNAs, that is highly expressed in monocytes/macrophages (18), is involved in the modulation of the NF-kB pathway, and its tissues and bloodstream levels are associated with a variety of inflammatory conditions. However, the roles of miRNAs in the anti-inflammatory responses of adiponectin and, in particular, the epigenetic mechanisms underlying the adiponectin modulation of cytokines expression need further investigation.…”

Section: Obesity Epigenetic Modifications and Inflammatory Modulationmentioning

confidence: 99%

Adiponectin Related Vascular and Cardiac Benefits in Obesity: Is There a Role for an Epigenetically Regulated Mechanism?

Fontanella

Rizzo

Surina

et al. 2021

Front. Cardiovasc. Med.

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In obesity, several epigenetic modifications, including histones remodeling, DNA methylation, and microRNAs, could accumulate and determine increased expression of inflammatory molecules, the adipokines, that in turn might induce or accelerate the onset and development of cardiovascular and metabolic disorders. In order to better clarify the potential epigenetic mechanisms underlying the modulation of the inflammatory response by adipokines, the DNA methylation profile in peripheral leukocytes of the promoter region of IL-6 and NF-kB genes and plasma miRNA-21 levels were evaluated in 356 healthy subjects, using quantitative pyrosequencing-based analysis, and correlated with plasma adiponectin levels, body fat content and the primary pro-inflammatory markers. In addition, correlation analysis of DNA methylation profiles and miRNA-21 plasma levels with intima-media thickness (IMT), a surrogate marker for early atherosclerosis, left ventricular mass (LVM), left ventricular ejection fraction (LVEF), and cardiac performance index (MPI) was also performed to evaluate any potential clinical implication in terms of cardiovascular outcome. Results achieved confirmed the role of epigenetics in the obesity-related cardiovascular complications and firstly supported the potential role of plasma miRNA-21 and IL-6 and NF-kB DNA methylation changes in nucleated blood cells as potential biomarkers for predicting cardiovascular risk in obesity. Furthermore, our results, showing a role of adiponectin in preventing epigenetic modification induced by increased adipose tissue content in obese subjects, provide new evidence of an additional mechanism underlying the anti-inflammatory properties and the cardiovascular benefits of adiponectin. The exact mechanisms underlying the obesity-related epigenetic modifications found in the blood cells and whether similar epigenetic changes reflect adipose and myocardial tissue modifications need to be further investigated in future experiments.

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Section: Obesity Epigenetic Modifications and Inflammatory Modulationmentioning

confidence: 99%

Adiponectin Related Vascular and Cardiac Benefits in Obesity: Is There a Role for an Epigenetically Regulated Mechanism?

Fontanella

Rizzo

Surina

et al. 2021

Front. Cardiovasc. Med.

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“…miR-21 is suggested as a marker in various cardiovascular diseases, including heart failure, atrial fibrillation, and dilated cardiomyopathy. Apart from cardiovascular diseases, numerous studies implicated miR-21 as a biomarker in many other diseases ranging from cancer, renal fibrosis, and diabetes (94). So far, miR-21 cannot be considered an ideal biomarker for a specific cardiomyopathy.…”

Section: Clinical Implications Of Mir-21mentioning

confidence: 99%

miR-21 in Human Cardiomyopathies

Surina

Fontanella

Scisciola

et al. 2021

Front. Cardiovasc. Med.

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miR-21 is a 22-nucleotide long microRNA that matches target mRNAs in a complementary base pairing fashion and regulates gene expression by repressing or degrading target mRNAs. miR-21 is involved in various cardiomyopathies, including heart failure, dilated cardiomyopathy, myocardial infarction, and diabetic cardiomyopathy. Expression levels of miR-21 notably change in both heart and circulation and provide cardiac protection after heart injury. In the meantime, miR-21 also tightly links to cardiac dysfunctions such as cardiac hypertrophy and fibrosis. This review focuses on the miR-21 expression pattern and its functions in diseased-heart and further discusses the feasibility of miR-21 as a biomarker and therapeutic target in cardiomyopathies.

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“…The functional role of these miRNAs will therefore be dependent on the local cellular contexture, and because the net effect on mRNA expression is highly unpredictable, GSE analysis cannot replace experimental validation. Furthermore, a miRNA may potentially have abnormal expression in multiple diseases, such as Mir-21, which has been shown to be up-regulated in 29 different diseases in addition to CRC 49 . Therefore, the functional role of the differentially expressed miRNAs is still not clear, but this work still represents an excellent starting point for further studies, as well as a basis for interpreting the, often contradictory, existing literature.…”

Section: Discussionmentioning

confidence: 99%

A microRNA Signature of Metastatic Colorectal Cancer

Høye

Fromm

Böttger

et al. 2020

Preprint

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BackgroundAlthough microRNAs (miRNAs) are involved in all hallmarks of cancer, miRNA dysregulation in the metastatic process remains poorly understood. We investigated the role of miRNAs in metastatic evolution of colorectal cancer (CRC) by analyzing smallRNA-seq datasets from primary CRC, metastatic locations (liver, lung and peritoneum), and corresponding adjacent tissues. Addressing main challenges of miRNA analysis, a bioinformatics pipeline was developed that contains bona fide miRNA annotations from MirGeneDB, utilizes the quality control software miRTrace, applies physiologically meaningful cutoffs and accounts for contribution of cell-type specific miRNAs and host tissue effects. ResultsTwo hundred-and-seventy-five miRNA sequencing datasets were analyzed, and after adjusting for the contribution of heterogeneity in cellular composition, strong signatures for primary and metastatic CRC were identified. The signature for primary CRC contained many previously known miRNAs with known functions. Deregulation of specific miRNAs was associated with individual metastatic sites, but the metastatic signatures contained overlapping miRNAs involved in key elements of the metastatic process, such as epithelial-to-mesenchymal transition and hypoxia. Notably, four of these miRNAs (MIR-8, MIR-10, MIR-375, MIR-210) belong to deeply conserved families present in many other organisms, triggering questions about their evolutionary functions and opportunities for experimental validation. Conclusion:Applying a meticulous pipeline for the analysis of smallRNA-seq data, miRNA signatures for primary and metastatic CRC were identified, contributing novel insights into miRNA involvement in CRC metastatic evolution and site-specific metastatic adaptations. New datasets can easily be included in this publicly available pipeline to continuously improve the knowledge in the field.

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miR-21: a non‐specific biomarker of all maladies

Cited by 153 publications

References 80 publications

Adiponectin Related Vascular and Cardiac Benefits in Obesity: Is There a Role for an Epigenetically Regulated Mechanism?

Adiponectin Related Vascular and Cardiac Benefits in Obesity: Is There a Role for an Epigenetically Regulated Mechanism?

miR-21 in Human Cardiomyopathies

A microRNA Signature of Metastatic Colorectal Cancer

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