MicroRNAs: role in cardiovascular biology and disease

2008 ◽  
Vol 114 (12) ◽  
pp. 699-706 ◽  
Author(s):  
Chunxiang Zhang

miRNAs (microRNAs) comprise a novel class of endogenous, small, non-coding RNAs that negatively regulate gene expression via degradation or translational inhibition of their target mRNAs. Recent studies have demonstrated that miRNAs are highly expressed in the cardiovascular system. Although we are currently in the initial stages of understanding how this novel class of gene regulators is involved in cardiovascular biological functions, a growing body of exciting evidence suggests that miRNAs are important regulators of cardiovascular cell differentiation, growth, proliferation and apoptosis. Moreover, miRNAs are key modulators of both cardiovascular development and angiogenesis. Consequently, dysregulation of miRNA function may lead to cardiovascular diseases. Indeed, several recent reports have demonstrated that miRNAs are aberrantly expressed in diseased hearts and vessels. Modulating these aberrantly expressed miRNAs has significant effects on cardiac hypertrophy, vascular neointimal lesion formation and cardiac arrhythmias. Identifying the roles of miRNAs and their target genes and signalling pathways in cardiovascular disease will be critical for future research. miRNAs may represent a new layer of regulators for cardiovascular biology and a novel class of therapeutic targets for cardiovascular diseases.

ExRNA ◽  
2019 ◽  
Vol 1 (1) ◽  
Author(s):  
Fangfang Jin ◽  
Zhigang Guo

Abstract The discovery of small non-coding RNAs, such as miRNA and piRNA, has dramatically changed our understanding of the role RNA plays in organisms. Recent studies show that a novel small non-coding RNA generated from cleavage of tRNA or pre-tRNA, called tRNA-derived small RNA (tsRNA), serves as a new regulator of gene expression. tsRNA has been determined participate in regulating some specific physiological and pathological processes. Although knowledge regarding the biological roles of miRNA and piRNA is expanding, whether tsRNAs play similar roles remains poorly understood. Here, we review the current knowledge regarding the mechanisms of action and biological functions of tsRNAs in intracellular, extracellular and intergenerational inheritance, and highlight the potential application of tsRNAs in human diseases, and present the current problems and future research directions.


2020 ◽  
Vol 9 (2) ◽  
pp. 86-91
Author(s):  
Mahta Moraghebi ◽  
Milad Rafat ◽  
Pegah Mousavi ◽  
Kianoosh Malekzadeh

MicroRNAs (miRNAs) constitute a large family of small non-coding RNAs which regulate gene expression at the surface following transcription. They are widely involved in many physiological and pathological processes including polycystic ovarian syndrome (PCOS). PCOS is an endocrine disorder in women. Currently, there is no comprehensive information about the role of miRNAs in PCOS. Thus, this paper has attempted to collate studies on miRNAs in order to determine important changes in their miRNA expression profile in the total blood, serum, plasma, follicular fluid, and granulosa cells in PCOS patients alongside the genes which are targeted for regulation by these miRNAs. This study presents a new approach for using miRNAs and their target genes for diagnosing and treating PCOS.


2021 ◽  
Vol 14 (2) ◽  
pp. 142-147
Author(s):  
Ruxandra Florentina Ionescu ◽  
◽  
Sanda Maria Cretoiu ◽  
◽  

The last decades showed a worrying increase in the evolution of cardiovascular diseases towards different stages of heart failure (HF), as a stigma of the western lifestyle. MicroRNAs (miRNAs), non-coding RNAs, which are approximately 22-nucleotide long, were shown to regulate gene expression at the post-transcriptional level and play a role in the pathogenesis and progression of HF. miRNAs research is of high interest nowadays, as these molecules display mechanisms of action that can influence the course of evolution of common chronic diseases, including HF. The potential of post-transcriptional regulation by miRNAs concerning the diagnosis, management, and therapy for HF represents a new promising approach in the accurate assessment of cardiovascular diseases. This review aims to assess the current knowledge of miRNAs in cardiovascular diseases, especially right-sided heart failure and hepatomegaly. Moreover, attention is focused on their role as potential molecular biomarkers and more promising aspects involving miRNAs as future therapeutic targets in the pathophysiology of HF.


2020 ◽  
Author(s):  
Fuhui Han ◽  
Jing Li ◽  
Nan Liu ◽  
Ranran Zhao ◽  
Lirong Liu ◽  
...  

Abstract Background: Intramuscular fat (IMF) content has become one of the most important indicators for measuring meat quality, and levels of IMF are affected by various genes. Long non-coding RNAs (lncRNAs) are widely expressed non-coding RNAs that play an important regulatory role in a variety of biological processes; however, research on the lncRNAs involved in sheep IMF deposition is still in its infancy. Aohan fine-wool sheep (AFWS), one of China's most important meat-hair, dual-purpose sheep breed, provides a great model for studying the role of lncRNAs in the regulation of IMF deposition. We identified lncRNAs by RNA sequencing in longissimus dorsi muscle (LDM) samples of sheep at two ages: 2 months (Mth-2) and 12 months (Mth-12). Results: We identified a total of 26,247 genes and 6,935 novel lncRNAs in LDM samples of sheep. Among these, 606 mRNAs and 408 lncRNAs were differentially expressed. We then compared the structural characteristics of lncRNAs and mRNAs. We obtained target genes of differentially expressed lncRNAs (DELs) and performed enrichment analyses using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). We found that target mRNAs were primarily enriched in lipid metabolism, lipid transport, regulation of primary metabolic processes and developmental pathways. Based on the results of important KEGG pathways, we obtained six candidate lncRNAs that potentially regulate lipid deposition and constructed an lncRNA-mRNA co-expression network that included MSTRG.792.1- SCD , MSTRG.8227.1- ACAA2 , MSTRG.10679.1- FADS2 , MSTRG.21942.1- PLA2G4E , MSTRG.21380.1- FZD4 and MSTRG.9270.1- ULK1 . We speculated that these candidate lncRNAs might play a role by regulating the expression of target genes. We randomly selected five mRNAs and five lncRNAs to verify the accuracy of the sequencing data by qRT-PCR. Conclusions: Our study provided a list of the lncRNAs and mRNAs related to intramuscular lipid deposition in sheep and laid a foundation for future research on regulatory mechanisms.


2017 ◽  
Vol 131 (15) ◽  
pp. 1923-1940 ◽  
Author(s):  
Steven Horsburgh ◽  
Nicola Fullard ◽  
Mathilde Roger ◽  
Abbie Degnan ◽  
Stephen Todryk ◽  
...  

The skin is the largest organ of the integumentary system and possesses a vast number of functions. Due to the distinct layers of the skin and the variety of cells which populate each, a tightly regulated network of molecular signals control development and regeneration, whether due to programmed cell termination or injury. MicroRNAs (miRs) are a relatively recent discovery; they are a class of small non-coding RNAs which possess a multitude of biological functions due to their ability to regulate gene expression via post-transcriptional gene silencing. Of interest, is that a plethora of data demonstrates that a number of miRs are highly expressed within the skin, and are evidently key regulators of numerous vital processes to maintain non-aberrant functioning. Recently, miRs have been targeted as therapeutic interventions due to the ability of synthetic ‘antagomiRs’ to down-regulate abnormal miR expression, thereby potentiating wound healing and attenuating fibrotic processes which can contribute to disease such as systemic sclerosis (SSc). This review will provide an introduction to the structure and function of the skin and miR biogenesis, before summarizing the literature pertaining to the role of miRs. Finally, miR therapies will also be discussed, highlighting important future areas of research.


2020 ◽  
Author(s):  
Fuhui Han ◽  
Jing Li ◽  
Nan Liu ◽  
Ranran Zhao ◽  
Lirong Liu ◽  
...  

Abstract Background: Intramuscular fat (IMF) content has become one of the most important indicators for measuring meat quality, and levels of IMF are affected by various genes. Long non-coding RNAs (lncRNAs) are widely expressed non-coding RNAs that play an important regulatory role in a variety of biological processes; however, research on the lncRNAs involved in sheep IMF deposition is still in its infancy. Aohan fine-wool sheep (AFWS), one of China's most important meat-hair, dual-purpose sheep breed, provides a great model for studying the role of lncRNAs in the regulation of IMF deposition. We identified lncRNAs by RNA sequencing in Longissimus thoracis et lumborum (LTL) samples of sheep at two ages: 2 months (Mth-2) and 12 months (Mth-12). Results: We identified a total of 26,247 genes and 6,935 novel lncRNAs in LTL samples of sheep. Among these, 199 mRNAs and 61 lncRNAs were differentially expressed. We then compared the structural characteristics of lncRNAs and mRNAs. We obtained target genes of differentially expressed lncRNAs (DELs) and performed enrichment analyses using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). We found that target mRNAs were enriched in metabolic processes and developmental pathways. Three pathways were significantly enriched, namely tight junction, glycosaminoglycan biosynthesis-heparan sulfate/heparin and lysosome. Based on the analysis of critical target genes, we obtained seven candidate lncRNAs that potentially regulated lipid deposition and constructed an lncRNA-mRNA co-expression network that included MSTRG.4051.3-FZD4,MSTRG.16157.3-ULK1, MSTRG.21053.3-PAQR3, MSTRG.19941.2-TPI1, MSTRG.12864.1-FHL1,MSTRG.2469.2-EXOC6 and MSTRG.21381.1-NCOA1. We speculated that these candidate lncRNAs might play a role by regulating the expression of target genes. We randomly selected five mRNAs and five lncRNAs to verify the accuracy of the sequencing data by qRT-PCR. Conclusions: Our study provided a list of the lncRNAs and mRNAs related to intramuscular lipid deposition in sheep and laid a foundation for future research on regulatory mechanisms.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Jaroslaw Thomas Dankert ◽  
Marc Wiesehöfer ◽  
Sven Wach ◽  
Elena Dilâra Czyrnik ◽  
Gunther Wennemuth

Abstract Prostate carcinoma (PCa) is the second most commonly diagnosed cancer in males worldwide. Among hereditary genetic mutations and nutrient factors, a link between the deregulation of microRNA (miRNA) expression and the development of prostate carcinoma is assumed. MiRNAs are small non-coding RNAs which post-transcriptionally regulate gene expression and which are involved in tumour development and progression as oncogenes or tumour suppressors. Although many genes could be confirmed as targets for deregulated miRNAs, the impact of differentially expressed miRNA and their regulatory target genes on prostate tumour development and progression are not fully understood yet. We could validate RBMS1, a barely described RNA-binding protein, as a new target gene for oncogenic miR-106b, which was identified as an induced miRNA in PCa. Further analysis revealed a loss of RBMS1 expression in prostate tumours compared to corresponding normal tissue. Overexpression of RBMS1 in DU145 and LNCaP prostate cancer cells resulted in diminished cell proliferation, colony forming ability as well as in retarded gap closing. Our results demonstrate for the first time a miR-106b dependent downregulation of RBMS1 in prostate carcinoma. Additionally, we show new tumour suppressive properties of RBMS1 whose observed loss may further elucidate the development of PCa.


Author(s):  
Sarubala Malayaperumal ◽  
Sushmitha Sriramulu ◽  
Ganesan Jothimani ◽  
Antara Banerjee ◽  
Surajit Pathak

: MicroRNAs (miRS) are a class of small non-coding RNAs which perform a crucial function in posttranscriptional gene regulation. Dysregulation of this microRNAs are associated with many types of cancer progression. In tumorigenesis, downregulated microRNAs might function as tumour suppressor by repressing onco- genes, whereas overexpressed miRs might function as oncogenes by suppressing tumour suppressor. Similarly, Metadherin (also known AEG-1/ LYRIC), is an oncogene, whose levels are found to be very high in various cancers and plays a crucial role in proliferation of cells and invasion. Our review focuses on the study which shows alteration of microRNA expression profile and suppression of carcinogenesis when MTDH/AEG-1 is targeted. It summarises about the studies where downregulation and upregulation AEG-1 and microRNAs respectively, alter the biological functions of the cell, such as proliferation and apoptosis. Studies have reported that AEG-1 can be direct or indirect target of microRNA which could provide a new-insight to know the underlying molecular mechanism and might contribute to the progress of new therapeutic strategies for the disease.


Cancers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2979
Author(s):  
Antonio Fernandez-Serra ◽  
David S. Moura ◽  
María Dolores Sanchez-Izquierdo ◽  
Silvia Calabuig-Fariñas ◽  
Maria Lopez-Alvarez ◽  
...  

MicroRNAs (miRNAs) are small non-coding RNAs that negatively regulate gene expression at the post-transcriptional level, and they have been described as being associated with tumor prognosis. Here, miRNA profiling was planned to explore new molecular prognostic biomarkers in localized intestinal high-risk GIST. Paraffin tumor blocks of 14 and 86 patients were used in the discovery and expansion sets, respectively. GeneChip miRNA v3.0 was employed to identify the miRNAs differentially expressed between relapsed and non-relapsed patient samples, which were validated in the expansion set, by qRT-PCR. RT2 Profiler PCR Array was used for the screening of let-7e targets. Expression levels were correlated with relapse-free survival and overall survival. In the discovery set, 39 miRNAs were significantly deregulated, let-7e and miR-550 being the most underexpressed and overexpressed miRNAs in the relapsed group, respectively. In the expansion set, the underexpression of let-7e or the overexpression of 4 of its target genes (ACVR1B, CASP3, COL3A1, and COL5A2) were statistically associated with worse relapse-free survival. The expression of let-7e and 4 of its target genes are potential prognostic biomarkers in high-risk localized intestinal GIST. The expression of these genes is a potential molecular tool useful for a more accurate prognosis in this subset of GIST patients.


2012 ◽  
Vol 153 (52) ◽  
pp. 2051-2059 ◽  
Author(s):  
Zsuzsanna Gaál ◽  
Éva Oláh

MicroRNAs are a class of small non-coding RNAs regulating gene expression at posttranscriptional level. Their target genes include numerous regulators of cell cycle, cell proliferation as well as apoptosis. Therefore, they are implicated in the initiation and progression of cancer, tissue invasion and metastasis formation as well. MicroRNA profiles supply much information about both the origin and the differentiation state of tumours. MicroRNAs also have a key role during haemopoiesis. An altered expression level of those have often been observed in different types of leukemia. There are successful attempts to apply microRNAs in the diagnosis and prognosis of acute lymphoblastic leukemia and acute myeloid leukemia. Measurement of the expression levels may help to predict the success of treatment with different kinds of chemotherapeutic drugs. MicroRNAs are also regarded as promising therapeutic targets, and can contribute to a more personalized therapeutic approach in haemato-oncologic patients. Orv. Hetil., 2012, 153, 2051–2059.


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