Key principles of miRNA involvement in human diseases

Giza, Dana Elena; Vasilescu, C; Calin, George A.

doi:10.15190/d.2014.26

Cited by 51 publications

(43 citation statements)

References 63 publications

(62 reference statements)

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“…As miRNAs are known to modulate many of their targets through mRNA transcript degradation [14], [36], we correlated the expression of miRNAs to the module eigengenes in order to evaluate their level of association. Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Furthermore, our integrated analyses of miRNA expression data with parallel gene expression levels using WCGNA identified co-expression modules that we were able to assign with biological functions and also correlate with clinical outcome data and fusion gene status. Given that miRNAs regulate the expression of many genes in a dynamic and cell context specific manner [14], these results provide a valuable framework and resource for further investigations of RMS.…”

Section: Discussionmentioning

confidence: 95%

“…MicroRNAs (miRNAs) are small (20–22 nt) RNA molecules that can alter cellular processes including proliferation, differentiation and apoptosis [14]. MiRNAs inhibit protein synthesis of specific genes by degrading specific mRNA species or hindering translation.…”

Section: Introductionmentioning

confidence: 99%

“…Specific mRNA degradation involves base-pairing to partially complementary sequences within the 3′ UTR [15] or other less frequently studied mechanisms including their binding to the 5′ UTR [16] and gene promoters regions [17]. Each miRNA potentially regulates hundreds of target gene products and it is suggested that the entire protein coding genome is regulated by miRNAs [14]. Individual miRNAs have been ascribed oncogenic or tumor suppressor roles in cancer and their roles can clearly be cell context specific [18].…”

Section: Introductionmentioning

confidence: 99%

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MicroRNA and gene co-expression networks characterize biological and clinical behavior of rhabdomyosarcomas

et al. 2017

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Rhabdomyosarcomas (RMS) in children and adolescents are heterogeneous sarcomas broadly defined by skeletal muscle features and the presence/absence of PAX3/7-FOXO1 fusion genes. MicroRNAs are small non-coding RNAs that regulate gene expression in a cell context specific manner. Sequencing analyses of microRNAs in 64 RMS revealed expression patterns separating skeletal muscle, fusion gene positive and negative RMS. Integration with parallel gene expression data assigned biological functions to 12 co-expression networks/modules that reassuringly included myogenic roles strongly correlated with microRNAs known in myogenesis and RMS development. Modules also correlated with clinical outcome and fusion status. Regulation of microRNAs by the fusion protein was demonstrated after PAX3-FOXO1 reduction, exemplified by miR-9-5p. MiR-9-5p levels correlated with poor outcome, even within fusion gene positive RMS, and were higher in metastatic versus non-metastatic disease. MiR-9-5p reduction inhibited RMS cell migration. Our findings reveal microRNAs in a regulatory framework of biological and clinical significance in RMS.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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MicroRNA and gene co-expression networks characterize biological and clinical behavior of rhabdomyosarcomas

et al. 2017

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“…They are possibly of importance in most of the diseases [24–26]. These ~22 nucleotide single-stranded RNA molecules mostly bind to 3’ UTR of specific target mRNA molecules and negatively regulate most gene expressions, either by translational repression or mRNA degradation [27,28].…”

Section: Introductionmentioning

confidence: 99%

miR-146a regulates glucose induced upregulation of inflammatory cytokines extracellular matrix proteins in the retina and kidney in diabetes

Chen¹,

Feng²,

Thomas³

et al. 2017

PLoS ONE

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Hyperglycemic damage to the endothelial cells (ECs) leads to increased synthesis of inflammatory cytokines. We have previously shown miR-146a downregulation in ECs and in the tissues of diabetic mice. Here we investigated the role of miR-146a, in the production of specific inflammatory cytokines and extracellular matrix (ECM) proteins in retina and kidneys in diabetes. We generated an endothelial specific miR-146a overexpressing transgenic mice (TG). We investigated these mice and wild type (WT) controls with or without streptozotocin (STZ) induced diabetes. Retinal and renal cortical tissues from the mice were examined for mRNAs for specific inflammatory markers, (ECM) proteins and inflammation inducible transcription factor by real time RT-PCR. Corresponding proteins, where possible, were examined using immunofluorescence or ELISA. In parallel, we examined ECs following incubation with various levels of glucose with or without miR-146a mimic transfection. In the retina and kidneys of WT mice with diabetes, increased expression of inflammatory markers (IL-6, TNFα, IL1β) in association augmented expression of ECM proteins (collagen 1αIV, fibronectin) and NF κB-P65 were observed, compared to WT non-diabetic controls. These changes were prevented in diabetic miR-146a TG mice along with retinal and renal functional and structural changes. In vitro studies showed similar changes in the ECs exposed to high glucose. Such changes were corrected in the cells following miR-146a mimic transfection. Further analyses of renal cortical tissues showed diabetes induced significant upregulation of two regulators of NFκB, namely Interleukin-1 associated Kinase 1 and tumour necrosis factor receptor associated factor. Such changes were prevented in diabetic TG animals. These data indicate that augmented production of inflammatory cytokines and ECM proteins in the retina and kidneys in diabetes are regulated through endothelium derived miR-146a. Identification of such novel mechanisms may potentially lead to the development of novel therapies.

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Deregulation of selected microRNAs in sinonasal carcinoma: Value of miR‐21 as prognostic biomarker in sinonasal squamous cell carcinoma

et al. 2017

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Background Tumors occurring in the sinonasal area are characterized by unfavorable outcome due to difficult diagnosis, treatment, and prognosis of the disease corresponding with the anatomic complexity of the area. Methods We used quantitative real‐time polymerase chain reaction (PCR) to compare relative expression of miR‐21, miR‐141, and miR‐200c in 70 formalin‐fixed, paraffin‐embedded samples of sinonasal carcinoma tissue (majority of squamous cell carcinoma [SCC] samples) with 17 control samples of sinonasal tissue. Results Our data showed significant upregulation of miR‐21 in sinonasal cancer tissue. Expression levels of miR‐141 and miR‐200c were below detectable levels in both sinonasal cancer samples and healthy tissue. Kaplan‐Meier analysis with log‐rank survival showed that patients with SCC with high expression of miR‐21 (highest quartile) had impaired survival close to reaching statistical significance (P = .0630). Conclusion Our results suggest that miR‐21 upregulation is involved in tumorigenesis of sinonasal carcinoma and that it is associated with poor prognosis. Thus, miR‐21 could be used as a valuable prognostic biomarker.

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Key principles of miRNA involvement in human diseases

Cited by 51 publications

References 63 publications

MicroRNA and gene co-expression networks characterize biological and clinical behavior of rhabdomyosarcomas

MicroRNA and gene co-expression networks characterize biological and clinical behavior of rhabdomyosarcomas

miR-146a regulates glucose induced upregulation of inflammatory cytokines extracellular matrix proteins in the retina and kidney in diabetes

Deregulation of selected microRNAs in sinonasal carcinoma: Value of miR‐21 as prognostic biomarker in sinonasal squamous cell carcinoma

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