The Role of miRNAs, miRNA Clusters, and isomiRs in Development of Cancer Stem Cell Populations in Colorectal Cancer

MicroRNAs (miRNAs or miRs) have a critical role in regulating stem cells (SCs) during development and altered expression can cause developmental defects and/or disease. Indeed, aberrant miRNA expression leads to wide-spread transcriptional dysregulation which has been linked to many cancers. Mounting evidence also indicates a role for miRNAs in the development of the cancer SC (CSC) phenotype. Our goal herein is to provide a review of: (i) current research on miRNAs and their targets in colorectal cancer (CRC), and (ii) miRNAs that are differentially expressed in colon CSCs. MicroRNAs can work in clusters or alone when targeting different SC genes to influence CSC phenotype. Accordingly, we discuss the specific miRNA cluster classifications and isomiRs that are predicted to target the ALDH1, CD166, BMI1, LRIG1, and LGR5 SC genes. miR-23b and miR-92A are of particular interest because our previously reported studies on miRNA expression in isolated normal versus malignant human colonic SCs showed that miR-23b and miR-92a are regulators of the LGR5 and LRIG1 SC genes, respectively. We also identify additional miRNAs whose expression inversely correlated with mRNA levels of their target genes and associated with CRC patient survival. Altogether, our deliberation on miRNAs, their clusters, and isomiRs in regulation of SC genes could provide insight into how dysregulation of miRNAs leads to the emergence of different CSC populations and SC overpopulation in CRC.

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Abstract 107: Mir-431 as a Potential Master Regulator in Angiotensin Ii-induced Vascular Injury

Hypertension ◽

10.1161/hyp.68.suppl_1.107 ◽

2016 ◽

Vol 68 (suppl_1) ◽

Author(s):

Kugeng Huo ◽

Tlili Barhoumi ◽

Julio C Fraulob-Aquino ◽

Chantal Richer ◽

Mathieu Lajoie ◽

...

Keyword(s):

Vascular Injury ◽

Molecular Networks ◽

Type I ◽

Mirna Cluster ◽

Mrna Levels ◽

Ang Ii ◽

Master Regulator ◽

Developmental Processes ◽

Altered Expression ◽

Total Rna

Objective: Vascular injury is an early manifestation and a cause of end-organ damage in hypertension. microRNAs (miRNAs) play an important role in cardiovascular disease, but their implication in vascular injury is remains unclear. We aim to use RNA sequencing (seq) and a systems biology approach to identify master regulators that mediate global gene expression changes in the course of vascular injury. Methods and Results: Ten week-old male C57BL/6 mice were infused or not with angiotensin (Ang) II (1 μg/kg/min, SC) for 14 days. Blood pressure (BP) was measured by telemetry. Total RNA was extracted from the mesenteric vasculature for total RNA and small RNA-seq. Differentially expressed (DE) miRNAs (23 up and 12 down) and mRNAs (550 up and 256 down) were identified (1.5-fold, q <0.05). Molecular networks were constructed to integrate predicted interactions between DE miRNAs and inversely expressed DE mRNAs and between DE transcription factors (TF) and DE genes. Gene enrichment analysis revealed DE mRNAs involved in extracellular matrix (ECM) and developmental processes regulated by DE miRNAs ( q <1.5E-11). Seventeen upregulated miRNAs are located in the miRNA cluster of the Dlk1-Dio3 region that is highly conserved in humans, 9 of which had expression levels correlated with BP ( P <0.05). Among those 9, miR-431 that ranked first as DE miRNA ( q <0.0005) and is 100% conserved in humans, and a conserved putative DE target, a BP-correlated ( P <0.05) TF ETS homologous factor ( Ehf ), which regulates numerous ECM genes including collagen type I α1 ( Col1a1 ), were selected for functional studies. Transfection of a miR-431 mimic in human aortic smooth muscle cells (HASMCs) decreased Ehf (0.1±0.1-fold, P <0.001) and increased Ehf -suppressing target Col1a1 (1.7±0.5-fold, P <0.001) mRNA levels. Transfection of a miR-431 inhibitor caused reciprocal effects ( P <0.05). Ehf siRNA knockdown increased Col1a1 (1.2±0.1-fold, P <0.001) mRNA levels. Conclusions: Ang II infusion altered expression of miRNAs in the Dlk1-Dio3 cluster and genes involved in ECM and developmental processes. miR-431 targets TF Ehf , which leads to increased Col1a1 in HASMCs. miR-431 may act as a master regulator for vascular injury and could be a potential therapeutic target.

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Fli1 Deficiency Induces CXCL6 Expression in Dermal Fibroblasts and Endothelial Cells, Contributing to the Development of Fibrosis and Vasculopathy in Systemic Sclerosis

The Journal of Rheumatology ◽

10.3899/jrheum.161092 ◽

2017 ◽

Vol 44 (8) ◽

pp. 1198-1205 ◽

Cited By ~ 13

Author(s):

Takashi Taniguchi ◽

Yoshihide Asano ◽

Kouki Nakamura ◽

Takashi Yamashita ◽

Ryosuke Saigusa ◽

...

Keyword(s):

Endothelial Cells ◽

Systemic Sclerosis ◽

Mrna Expression ◽

Target Genes ◽

Critical Role ◽

Dermal Fibroblasts ◽

Vascular Involvement ◽

Digital Ulcers ◽

Mrna Levels ◽

Predisposing Factor

Objective.CXCL6, a chemokine with proangiogenic property, is reported to be involved in vasculopathy associated with systemic sclerosis (SSc). We investigated the contribution of CXCL6 to SSc development by focusing on the association of friend leukemia virus integration 1 (Fli1) deficiency, a potential predisposing factor of SSc, with CXCL6 expression and clinical correlation of serum CXCL6 levels.Methods.mRNA levels of target genes and the binding of Fli1 to the CXCL6 promoter were evaluated by quantitative reverse transcription-PCR and chromatin immunoprecipitation, respectively. Serum CXCL6 levels were determined by ELISA.Results.FLI1 siRNA significantly enhanced CXCL6 mRNA expression in human dermal fibroblasts and human dermal microvascular endothelial cells, while Fli1 haploinsufficiency significantly suppressed CXCL6 mRNA expression in murine peritoneal macrophages stimulated with lipopolysaccharide. Supporting a critical role of Fli1 deficiency to induce SSc-like phenotypes, CXCL6 mRNA expression was higher in SSc dermal fibroblasts than in normal dermal fibroblasts. Importantly, Fli1 bound to the CXCL6 promoter in dermal fibroblasts, endothelial cells, and THP-1 cells. In patients with SSc, serum CXCL6 levels correlated positively with the severity of dermal and pulmonary fibrosis and were elevated in association with cardiac and pulmonary vascular involvement and cutaneous vascular symptoms, including Raynaud phenomenon, digital ulcers (DU)/pitting scars, and telangiectasia. Especially, serum CXCL6 levels were associated with DU/pitting scars and heart involvement by multiple regression analysis.Conclusion.CXCL6 expression is upregulated by Fli1 deficiency in fibroblasts and endothelial cells, potentially contributing to the development of fibrosis and vasculopathy in the skin, lung, and heart of SSc.

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Analysis of Microvesicle Microrna Expression Profiles and Their Functional Roles in ALL Subtypes

Blood ◽

10.1182/blood.v118.21.1488.1488 ◽

2011 ◽

Vol 118 (21) ◽

pp. 1488-1488

Author(s):

Xiaomei Chen ◽

Wei Xiong ◽

Xiangjun Chen ◽

Cong Lu ◽

Fang Liu ◽

...

Keyword(s):

Cell Line ◽

Mirna Expression ◽

Target Genes ◽

Expression Profiles ◽

Jurkat Cells ◽

Negative Regulator ◽

Altered Expression ◽

Normal Peripheral Blood ◽

Potential Target ◽

Mirna Expression Profiles

Abstract Abstract 1488 Microvesicles (MVs) released by leukemia cells constitute an important part of the leukemia microenvironment. As a cell-to-cell communication tool, MVs transfer microRNA(miRNA) between cells. MVs miRNAs may be valuable not only as a diagnostic tool but may also provide an insight in the role of miRNAs playing in the underlying of pathophysiologic processes of various leukemia. It is worth evaluating whether MVs possess some unique miRNA content depending on their corresponding leukemia origin that could be applicable in diagnosis. Hence, we determined the miRNA expression profiles of ALL-derived MVs using Agilent miRNA microarray analysis. The five miRNAs obtained by microarray profiling were validated using real-time PCR. The putative target genes were predicted by bioformation software. Here, we provided MVs miRNA patterns derived from the healthy controls, B-ALL cell line Nalm 6 cells and T-ALL cell line Jurkat cells. We identified 182 dysregulated miRNAs in MVs derived from Nalm 6 cells as compared with MVs from normal controls (P<0.05); both up regulated(123/182) and down regulated(59/182) expressions were observed. Likewise 166 miRNAs were significantly differentially expressed in MVs derived from Jurkat cells versus MVs from normal peripheral blood (P<0.05), 114 miRNAs of which (114/166) were up expression and 52 miRNAs (52/166) were down expression. We also fould that 44 miRNAs were only detected in B-ALL-derived MVs. MiR-1290, miR-1246, miR-1268, miR-1226, and miR-424 were top 5 expressed in Nalm 6 derived MVs, suggesting that those miRNAs may play an important role in B-ALL. We observed that 16 miRNAs detected only in T cell derived MVs. MiR-96 is up regulated in MVs from T-ALL cells but not expressed in B-ALL. Specific and functional target sites for miR-96, exist in the 3'-UTR of the miRNA that encodes the putative tumor suppressor transcription factor FOXO1. The expression signatures of miR-96 could discriminate B-ALL from T-ALL. In contrast, the MVs from B-ALL cell line, shared 100 miRNAs with MVs from T-ALL cell line, suggestting that those miRNAs play roles in both B-and T-ALL. Of 100 miRNAs, 99 miRNAs were high expression, indicating that miRNAs were active in ALL. This obsearvation suggusted that miRNA differential expression in MVs were partially significantly related to subtypes of acute lymphoblastic leukemia. Intriguing is that miR1290 is top higher expression both in MVs derived from Nalm6 cells and from Jurkat cells; miR-1290 is 475-fold higher expressed in Nalm 6 derived MVs versus MVs from normal cells, whereas this miRNA is 245-fold higher expressed in Jurkat cells. Five of these miRNAs were selected to be further assayed and validated by PCR. The qRT-PCR results correlated well with the microarray data. In addition, we found seven miRNAs(miR-148b, miR-484, miR-let-7f, let-7a, miR-223, miR16 and miR-27b) were located near the 11q23 chromosomal region. With bioinformatic tools (TargetScan), we predicted potential target genes for those miRNAs that exhibited altered expression in MVs from B-ALL and T-ALL. The p85 subunit of phosphatidylinositol 3-kinase (PI3-K) was found to be a potential target of miR-320. Of particular interest, we found that protein tyrosine phosphatase-like member b (PTPLB) may be a potential target of miR-1290. The 474-fold increase in miR-1290 in MVs from Nalm 6 cells, indicating that miR-1290 may participate in the modulation of leukemia by targeting PTPLB, a specific, negative regulator of p210 bcr-abl signal. In conclusion, we identified miRNAs and found that miRNA expression profiles were ALL subtype-specific. Altered miRNA expression levels may lead to an inappropriate expression of target oncoproteins or target tumor suppressors, thereby facilitating the development of leukemia. These findings expanded the potential diagnostic markers of leukemia and provided useful information to ALL pathogenesis. Disclosures: No relevant conflicts of interest to declare.

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MicroRNA-142-3p Inhibits Tumorigenesis of Colorectal Cancer via Suppressing the Activation of Wnt Signaling by Directly Targeting to β-Catenin

Frontiers in Oncology ◽

10.3389/fonc.2020.552944 ◽

2021 ◽

Vol 10 ◽

Author(s):

Peng Liu ◽

Fuao Cao ◽

Jinke Sui ◽

Yonggang Hong ◽

Qizhi Liu ◽

...

Keyword(s):

Colorectal Cancer ◽

Cell Proliferation ◽

Wnt Signaling ◽

Mirna Expression ◽

Colony Formation ◽

Expression Profiles ◽

Underlying Mechanism ◽

Luciferase Assay ◽

Nuclear Accumulation ◽

Altered Expression

BackgroundAltered expression profile of microRNAs (miRNAs) was reported to be associated with colorectal cancer (CRC). The aims of this study are to identify the changed miRNAs in the plasma of CRC patients and explore the underlying mechanism of these miRNAs during tumorigenesis.MethodsPlasma miRNA expression profiles were compared between healthy people and CRC patients. MiRNA expression was measured using quantitative real-time PCR. Colony formation and MTT assays were used to test cell proliferation. Luciferase assay, immunohistochemistry and Western blotting were employed to explore the molecular mechanism.ResultsMiR-142-3p level was found as the most significantly repressed miRNA in CRC patients. Overexpression of miR-142-3p dramatically repressed colony formation and cell proliferation of both HT29 and HCT116 cells while inhibition of miR-142-3p promoted those of the cells. Interestingly, overexpression of miR-142-3p reduced the level and nuclear accumulation of β-catenin. We further observed that miR-142-3p remarkably inhibited the transcriptional activity of β-catenin gene (CTNNB1). However, mutations in the predicted binding sites blocked this inhibition, suggesting that miR-142-3p may directly bind to the mRNA of β-catenin.ConclusionIn conclusion, we identified miR-142-3p exerts its function as a tumor suppressor through blocking the activation of Wnt signaling by directly targeting to CTNNB1.

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ARID1A loss derepresses human endogenous retrovirus-H to modulate BRD4-dependent transcription

10.1101/2021.06.28.450127 ◽

2021 ◽

Author(s):

Chunhong Yu ◽

Xiaoyun Lei ◽

Fang Chen ◽

Song Mao ◽

Lu Lv ◽

...

Keyword(s):

Colorectal Cancer ◽

Tumor Growth ◽

Tumor Suppressors ◽

Target Genes ◽

Critical Role ◽

Endogenous Retrovirus ◽

Early Embryogenesis ◽

Human Endogenous Retrovirus ◽

Regulatory Sequences ◽

3D Architecture

The transposable elements (TEs) through evolutionary exaptation have become an integral part of human genome, offering ample regulatory sequences and shaping chromatin 3D architecture. While the functional impacts of TE-derived sequences on early embryogenesis are recognized, their role in malignancy has only started to emerge. Here we show that many TEs, especially the pluripotency-related endogenous retrovirus H (HERVH), are abnormally activated in colorectal cancer (CRC) samples. The transcriptional upregulation of HERVH is associated with mutations of several tumor suppressors including ARID1A. Knockout of ARID1A in CRC cells leads to increased accessibility at HERVH loci and enhanced transcription, which is dependent on ARID1B. Suppression of HERVH in CRC cells and patient-derived organoids impairs tumor growth. Mechanistically, HERVH transcripts colocalize with nuclear BRD4 foci, modulate their dynamics, and co-regulate many target genes. Altogether, we uncover a critical role for ARID1A in restraining HERVH, which can promote tumorigenesis by stimulating BRD4-dependent transcription when ARID1A is mutated.

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ChrXq27.3 miRNA cluster functions in cancer development

Journal of Experimental & Clinical Cancer Research ◽

10.1186/s13046-021-01910-0 ◽

2021 ◽

Vol 40 (1) ◽

Author(s):

Kosuke Yoshida ◽

Akira Yokoi ◽

Yusuke Yamamoto ◽

Hiroaki Kajiyama

Keyword(s):

Cancer Progression ◽

Target Genes ◽

Epithelial Mesenchymal Transition ◽

Mature Mirnas ◽

Mirna Cluster ◽

Mesenchymal Transition ◽

Normal Tissues ◽

Mirna Clusters ◽

Cancer Tissues ◽

Encoding Genes

AbstractMicroRNAs (miRNAs) regulate the expression of their target genes post-transcriptionally; thus, they are deeply involved in fundamental biological processes. miRNA clusters contain two or more miRNA-encoding genes, and these miRNAs are usually coexpressed due to common expression mechanisms. Therefore, miRNA clusters are effective modulators of biological pathways by the members coordinately regulating their multiple target genes, and an miRNA cluster located on the X chromosome q27.3 region has received much attention in cancer research recently. In this review, we discuss the novel findings of the chrXq27.3 miRNA cluster in various types of cancer.The chrXq27.3 miRNA cluster contains 30 mature miRNAs synthesized from 22 miRNA-encoding genes in an ~ 1.3-Mb region. The expressions of these miRNAs are usually negligible in many normal tissues, with the male reproductive system being an exception. In cancer tissues, each miRNA is dysregulated, compared with in adjacent normal tissues. The miRNA-encoding genes are not uniformly distributed in the region, and they are further divided into two groups (the miR-506-514 and miR-888-892 groups) according to their location on the genome. Most of the miRNAs in the former group are tumor-suppressive miRNAs that are further downregulated in various cancers compared with normal tissues. miR-506-3p in particular is the most well-known miRNA in this cluster, and it has various tumor-suppressive functions associated with the epithelial–mesenchymal transition, proliferation, and drug resistance. Moreover, other miRNAs, such as miR-508-3p and miR-509-3p, have similar tumor-suppressive effects. Hence, the expression of these miRNAs is clinically favorable as prognostic factors in various cancers. However, the functions of the latter group are less understood. In the latter group, miR-888-5p displays oncogenic functions, whereas miR-892b is tumor suppressive. Therefore, the functions of the miR-888–892 group are considered to be cell type- or tissue-specific.In conclusion, the chrXq27.3 miRNA cluster is a critical regulator of cancer progression, and the miRNAs themselves, their regulatory mechanisms, and their target genes might be promising therapeutic targets.

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Variation of MicroRNA Expression in the Human Placenta Driven by Population Identity and Sex of the Newborn

10.21203/rs.3.rs-48907/v1 ◽

2020 ◽

Author(s):

Song Guo ◽

Shuyun Huang ◽

Xi Jiang ◽

Haiyang Hu ◽

Dingding Han ◽

...

Keyword(s):

Mirna Expression ◽

Target Genes ◽

South Asians ◽

Human Populations ◽

Human Tissues ◽

Expression Variation ◽

Quantitative Expression ◽

Unified Protocol ◽

Novel Mirna ◽

Mirna Clusters

Abstract BackgroundAnalysis of lymphocyte cell lines revealed substantial differences in the expression of mRNA and microRNA (miRNA) among human populations. The extent of such population-associated differences in actual human tissues remains largely unexplored. The placenta is one of the few solid human tissues that can be collected in substantial numbers in a controlled manner, enabling quantitative analysis of transient biomolecules such as RNA transcripts. Here, we analyzed microRNA (miRNA) expression in human placental samples derived from 36 individuals representing four genetically distinct human populations: African Americans, European-Americans, South Asians, and East Asians. All samples were collected at the same hospital following a unified protocol, thus minimizing potential biases that might influence the results.ResultsSequence analysis of the miRNA fraction yielded 938 annotated and 70 novel miRNA transcripts expressed in the placenta. Of them, 82 (9%) of annotated and 11 (16%) of novel miRNAs displayed quantitative expression differences among populations, generally reflecting reported genetic and mRNA-expression-based distances. Several co-expressed miRNA clusters stood out from the rest of the population-associated differences in terms of miRNA evolutionary age, tissue-specificity, and disease-association characteristics. Among three non-environmental influenced demographic parameters, the second largest contributor to miRNA expression variation after population was the sex of the newborn, with 32 miRNAs (3% of detected) exhibiting significant expression differences depending on whether the newborn was male or female. Male-associated miRNAs were evolutionarily younger and correlated inversely with the expression of target mRNA involved in neuron-related functions. In contrast, both male and female-associated miRNAs appeared to mediate different types of hormonal responses. Demographic factors further affected reported imprinted expression of 66 placental miRNAs: the imprinting strength correlated with the mother’s weight, but not height. ConclusionsOur results showed that among 12 assessed demographic variables, population affiliation and fetal sex had a substantial influence on miRNA expression variation among human placental samples. The effect of newborn-sex-associated miRNA differences further led to expression inhibition of the target genes clustering in specific functional pathways. By contrast, population-driven miRNA differences might mainly represent neutral changes with minimal functional impacts.

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Genome-Wide Uncovering of STAT3-Mediated miRNA Expression Profiles in Colorectal Cancer Cell Lines

BioMed Research International ◽

10.1155/2014/187105 ◽

2014 ◽

Vol 2014 ◽

pp. 1-11 ◽

Cited By ~ 2

Author(s):

Jufeng Zhang ◽

Xia Luo ◽

Huiming Li ◽

Ling Deng ◽

Ying Wang

Keyword(s):

Colorectal Cancer ◽

Cell Lines ◽

Mirna Expression ◽

Target Genes ◽

Expression Profiles ◽

Small Noncoding Rnas ◽

Genome Wide ◽

Go Enrichment ◽

Mirna Expression Profiles ◽

Mirna Expression Profiling

Colorectal cancer (CRC) is one of the most common malignancies resulting in high mortality worldwide. Signal transducer and activator of transcription 3 (STAT3) is an oncogenic transcription factor which is frequently activated and aberrantly expressed in CRC. MicroRNAs (miRNAs) are a class of small noncoding RNAs which play important roles in many cancers. However, little is known about the global miRNA profiles mediated by STAT3 in CRC cells. In the present study, we applied RNA interference to inhibit STAT3 expression and profiled the miRNA expression levels regulated by STAT3 in CRC cell lines with deep sequencing. We found that 26 and 21 known miRNAs were significantly overexpressed and downexpressed, respectively, in the STAT3-knockdown CRC cell line SW480 (SW480/STAT3-siRNA) compared to SW480 transfected with scrambled siRNAs (SW480/siRNA-control). The miRNA expression profiling was then validated by quantitative real-time PCR for selected known miRNAs. We further predicted the putative target genes for the dysregulated miRNAs and carried out functional annotation including GO enrichment and KEGG pathway analysis for selected miRNA targets. This study directly depicts STAT3-mediated miRNA profiles in CRC cells, which provides a possible way to discover biomarkers for CRC therapy.

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Highly Ordered Architecture of MicroRNA Cluster

BioMed Research International ◽

10.1155/2013/463168 ◽

2013 ◽

Vol 2013 ◽

pp. 1-4 ◽

Cited By ~ 3

Author(s):

Bing Shi ◽

Mingxuan Zhu ◽

Shuang Liu ◽

Mandun Zhang

Keyword(s):

Mirna Expression ◽

Expression Patterns ◽

Expression Level ◽

Mirna Cluster ◽

Microrna Cluster ◽

Mirna Clusters ◽

Mirna Expression Level ◽

Cluster A ◽

The Relationship

Although it is known that the placement of genes in a cluster may be critical for proper expression patterns, it remains largely unclear whether the orders of members in an miRNA cluster have biological insights. By investigating the relationship between expression and orders for miRNAs from the oncogenic miR-17-92 cluster, we observed a highly ordered architecture in this cluster. A significant correlation between miRNA expression level and its placement was revealed. More importantly, the placement of these miRNAs is associated with their dysregulation in cancer. Here, we presented the opinion that miRNA clusters are not arranged randomly but show highly ordered architectures, which may have critical roles in physiology and pathology.

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Expression of microRNAs and their target mRNAs in human stem cell-derived cardiomyocyte clusters and in heart tissue

Physiological Genomics ◽

10.1152/physiolgenomics.00074.2010 ◽

2011 ◽

Vol 43 (10) ◽

pp. 581-594 ◽

Cited By ~ 21

Author(s):

Jane Synnergren ◽

Caroline Améen ◽

Anders Lindahl ◽

Björn Olsson ◽

Peter Sartipy

Keyword(s):

Stem Cell ◽

Mrna Expression ◽

Mirna Expression ◽

Target Genes ◽

Cardiac Tissue ◽

Heart Tissue ◽

Mrna Levels ◽

Regulatory Pathways ◽

Adult Heart ◽

Starting Point

Recent studies have shown that microRNAs (miRNAs) act as posttranscriptional regulators and that they play important roles during heart development and in cardiac function. Thus, they may provide new means of altering stem cell fate and differentiation processes. However, information about the correlation between global miRNA and mRNA expression in cardiomyocyte clusters (CMCs) derived from human embryonic stem cells (hESC) and in fetal and adult heart tissue is lacking. In the present study the global miRNA and mRNA expression in hESC-derived CMCs and in fetal and adult heart tissue was investigated in parallel using microarrays. Target genes for the differentially expressed miRNAs were predicted using computational methods, and the concordance in miRNA expression and mRNA levels of potential target genes was determined across the experimental samples. The biology of the predicted target genes was further explored regarding their molecular functions and involvement in known regulatory pathways. A clear correlation between the global miRNA expression and corresponding target mRNA expression was observed. Using three different sources of cardiac tissue-like samples, we defined the similarities between in vitro hESC-derived CMCs and their in vivo counterparts. The results are in line with previously reported observations that miRNAs repress mRNA expression and additionally identify a number of novel miRNAs with potential important roles in human cardiac tissue. The concordant miRNA expression pattern observed among all the cardiac tissue-like samples analyzed here provide a starting point for future ambitious studies aiming towards assessment of the functional roles of specific miRNAs during cardiomyocyte differentiation.

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