scholarly journals MicroRNA-202 Induces Myoblast to Myocyte Differentiation through Targeting Rock-1

2021 ◽  
Author(s):  
Maryam Honardoost ◽  
Mahsa Bourbour ◽  
Ehsan Arefian
Keyword(s):  
Target Genes ◽  
Horse Serum ◽  
Expression Patterns ◽  
C2c12 Cell ◽  
Inhibitory Effect ◽  
Luciferase Assay ◽  
Differentiation Process ◽  
Myocyte Differentiation ◽  
Non Coding Rnas ◽  
The Impact

Abstract The expression patterns of microRNAs (small non-coding RNAs) are altered in many biological processes such as myogenesis. In this study, we aimed to investigate the impact of predicted miR-202, its target genes Akt2 and Rock-1 as a potential regulator of myoblast in the myocyte differentiation process using the C2C12 cell line. After confirmation of the differentiation process induced by 3% horse serum, the expression level of miRNA and its targets were evaluated. In the following, a luciferase assay was conducted to approve the effect of miRNA on its target. Our results indicated that miR-202 and Akt2 were significantly up-regulated during differentiation, while Rock-1 was downregulated. Co-transfection of miRNA with psiCHECK2-Rock-1 significantly presented that Rock-1 was directly targeted by miR-202. On the contrary, miR-202 has failed to enforce its inhibitory effect on Akt2 expression. In particular, miR-202 seems to be a regulator of muscle differentiation pathway thought targeting Rock-1.

scholarly journals RNAseq Studies Reveal Distinct Transcriptional Response to Vitamin a (VA) Deficiency in Small Intestine (SI) versus Colon, Discovering Novel VA-regulated Genes (P15-002-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Zhi Chai ◽  
Yafei Lyu ◽  
Qiuyan Chen ◽  
Cheng-Hsin Wei ◽  
Lindsay Snyder ◽  
...  
Keyword(s):  
Gene Expression ◽  
Small Intestine ◽  
Vitamin A ◽  
Target Genes ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Differentially Expressed Gene ◽  
Gene Expression Profiles ◽  
Illumina Hiseq ◽  
The Impact

Abstract Objectives To characterize and compare the impact of vitamin A (VA) deficiency on gene expression patterns in the small intestine (SI) and the colon, and to discover novel target genes in VA-related biological pathways. Methods vitamin A deficient (VAD) mice were generated by feeding VAD diet to pregnant C57/BL6 dams and their post-weaning offspring. Total mRNA extracted from SI and colon were sequenced using Illumina HiSeq 2500 platform. Differentially Expressed Gene (DEG), Gene Ontology (GO) enrichment, and Weighted Gene Co-expression Network Analysis (WGCNA) were performed to characterize expression patterns and co-expression patterns. Results The comparison between vitamin A sufficient (VAS) and VAD groups detected 49 and 94 DEGs in SI and colon, respectively. According to GO information, DEGs in the SI demonstrated significant enrichment in categories relevant to retinoid metabolic process, molecule binding, and immune function. Immunity related pathways, such as “humoral immune response” and “complement activation,” were positively associated with VA in SI. On the contrary, in colon, “cell division” was the only enriched category and was negatively associated with VA. WGCNA identified modules significantly correlated with VA status in SI and in colon. One of those modules contained five known retinoic acid targets. Therefore we have prioritized the other module members (e.g., Mbl2, Mmp9, Mmp13, Cxcl14 and Pkd1l2) to be investigated as candidate genes regulated by VA. Comparison of co-expression modules between SI and colon indicated distinct VA effects on these two organs. Conclusions The results show that VA deficiency alters the gene expression profiles in SI and colon quite differently. Some immune-related genes (Mbl2, Mmp9, Mmp13, Cxcl14 and Pkd1l2) may be novel targets under the control of VA in SI. Funding Sources NIH training grant and NIH research grant. Supporting Tables, Images and/or Graphs

scholarly journals The PARP Inhibitor Olaparib Modulates the Transcriptional Regulatory Networks of Long Non-Coding RNAs during Vasculogenic Mimicry

Cells ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 2690
Author(s):  
Mónica Fernández-Cortés ◽  
Eduardo Andrés-León ◽  
Francisco Javier Oliver
Keyword(s):  
Transcription Factors ◽  
Binding Sites ◽  
Regulatory Networks ◽  
Target Genes ◽  
Parp Inhibitor ◽  
Vasculogenic Mimicry ◽  
Transcriptome Profiling ◽  
Key Species ◽  
Non Coding Rnas ◽  
The Impact

In highly metastatic tumors, vasculogenic mimicry (VM) involves the acquisition by tumor cells of endothelial-like traits. Poly-(ADP-ribose) polymerase (PARP) inhibitors are currently used against tumors displaying BRCA1/2-dependent deficient homologous recombination, and they may have antimetastatic activity. Long non-coding RNAs (lncRNAs) are emerging as key species-specific regulators of cellular and disease processes. To evaluate the impact of olaparib treatment in the context of non-coding RNA, we have analyzed the expression of lncRNA after performing unbiased whole-transcriptome profiling of human uveal melanoma cells cultured to form VM. RNAseq revealed that the non-coding transcriptomic landscape differed between olaparib-treated and non-treated cells: olaparib significantly modulated the expression of 20 lncRNAs, 11 lncRNAs being upregulated, and 9 downregulated. We subjected the data to different bioinformatics tools and analysis in public databases. We found that copy-number variation alterations in some olaparib-modulated lncRNAs had a statistically significant correlation with alterations in some key tumor suppressor genes. Furthermore, the lncRNAs that were modulated by olaparib appeared to be regulated by common transcription factors: ETS1 had high-score binding sites in the promoters of all olaparib upregulated lncRNAs, while MZF1, RHOXF1 and NR2C2 had high-score binding sites in the promoters of all olaparib downregulated lncRNAs. Finally, we predicted that olaparib-modulated lncRNAs could further regulate several transcription factors and their subsequent target genes in melanoma, suggesting that olaparib may trigger a major shift in gene expression mediated by the regulation lncRNA. Globally, olaparib changed the lncRNA expression landscape during VM affecting angiogenesis-related genes.

scholarly journals Distribution and vulnerability of transcriptional outputs across the genome in Myc-amplified medulloblastoma cells

2021 ◽  
Author(s):  
Rui Yang ◽  
Wenzhe Wang ◽  
Meichen Dong ◽  
Kristen Roso ◽  
Paula Greer ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Tumor Cells ◽  
Target Genes ◽  
De Novo ◽  
Inhibitory Effect ◽  
Nucleotide Synthesis ◽  
High Level ◽  
The Impact

Myc plays a central role in tumorigenesis by orchestrating the expression of genes essential to numerous cellular processes1-4. While it is well established that Myc functions by binding to its target genes to regulate their transcription5, the distribution of the transcriptional output across the human genome in Myc-amplified cancer cells, and the susceptibility of such transcriptional outputs to therapeutic interferences remain to be fully elucidated. Here, we analyze the distribution of transcriptional outputs in Myc-amplified medulloblastoma (MB) cells by profiling nascent total RNAs within a temporal context. This profiling reveals that a major portion of transcriptional action in these cells was directed at the genes fundamental to cellular infrastructure, including rRNAs and particularly those in the mitochondrial genome (mtDNA). Notably, even when Myc protein was depleted by as much as 80%, the impact on transcriptional outputs across the genome was limited, with notable reduction mostly only in genes involved in ribosomal biosynthesis, genes residing in mtDNA or encoding mitochondria-localized proteins, and those encoding histones. In contrast to the limited direct impact of Myc depletion, we found that the global transcriptional outputs were highly dependent on the activity of Inosine Monophosphate Dehydrogenases (IMPDHs), rate limiting enzymes for de novo guanine nucleotide synthesis and whose expression in tumor cells was positively correlated with Myc expression. Blockage of IMPDHs attenuated the global transcriptional outputs with a particularly strong inhibitory effect on infrastructure genes, which was accompanied by the abrogation of MB cells proliferation in vitro and in vivo. Together, our findings reveal a real time action of Myc as a transcriptional factor in tumor cells, provide new insight into the pathogenic mechanism underlying Myc-driven tumorigenesis, and support IMPDHs as a therapeutic vulnerability in cancer cells empowered by a high level of Myc oncoprotein.

miR-193b-3p Promotes Proliferation of Goat Myoblast Through Directly Targeting IGF2BP1 and Activating Its Transcription

2020 ◽  
Author(s):  
Li Li ◽  
Xiao Zhang ◽  
Hailong Yang ◽  
Xiaoli Xu ◽  
Yuan Chen ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Development ◽  
Target Genes ◽  
Expression Patterns ◽  
Muscle Disease ◽  
Cell Counting ◽  
C2c12 Myoblast ◽  
Recognition Element ◽  
Myoblast Proliferation ◽  
The Impact

Abstract BackgroundAs a well-known cancer-related miRNA, miR-193b-3p is enriched in skeletal muscle but dysregulated in muscle disease. However, mechanism underpinning has not been addressed so far. MethodsHere, we probed the impact of miR-193b-3p on myogenesis by mainly using goat tissues and skeletal muscle satellite cells (MuSCs), with combined methods including RNA-seq to profile the transcriptome affected by miR-193b-3p, cell-counting kit-8 (CCK-8) and 5-ethynyl-2'-deoxyuridine (EdU) for cell proliferation assay, and RNA-RNA dual-labeled fluorescence in situ hybridization (FISH) for RNA colocalization. ResultsmiR-193b-3p is highly enriched in goat skeletal muscles, and ectopic miR-193b-3p promotes MuSCs proliferation and differentiation. Moreover, insulin-like growth factor-2 mRNA-binding protein 1 (IGF2BP1) is the most activated insulin signaling genes when overexpression miR-193b-3p and the miRNA recognition element (MRE) within IGF1BP1 3ʹ untranslated region (UTR) is indispensable for its activation caused by miR-193b-3p. Consistently, expression patterns and function of IGF2BP1 were similar to those of miR-193b-3p in tissues and MuSCs. While the overexpression of miR-193b-3p failed to induce pax7 expression and myoblast proliferation when IGF2BP1 knockdown. Furthermore, miR-193b-3p destabilized IGF2BP1 mRNA but unexpectedly promoted levels of IGF2BP1 heteronuclear RNA (hnRNA) dramatically. Moreover, miR-193b-3p could enhance fly luciferase activity when inserted upstream of its promoter, and induce neighboring genes of itself. However, miR-193b-3p inversely regulated IGF2BP1 and myoblast proliferation in mouse C2C12 myoblast. These data unveil that goat miR-193b-3p promotes myoblast proliferation via activating IGF2BP1 by binding on its 3ʹ UTR.ConclusionsOur novel findings highlight the positive regulation between miRNA and its target genes in muscle development, which further extends the repertoire of miRNA functions.

scholarly journals BIOL-10. DISTRIBUTION AND VULNERABILITY OF TRANSCRIPTIONAL OUTPUTS ACROSS THE GENOME IN MYC-AMPLIFIED MEDULLOBLASTOMA CELLS

2021 ◽  
Vol 23 (Supplement_1) ◽  
pp. i5-i5
Author(s):  
Rui Yang ◽  
Wenzhe Wang ◽  
Meichen Dong ◽  
Kristen Roso ◽  
Xuhui Bao ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Target Genes ◽  
De Novo ◽  
Inhibitory Effect ◽  
Nucleotide Synthesis ◽  
Expression Of Genes ◽  
High Level ◽  
The Impact

Abstract Myc plays a central role in tumorigenesis by orchestrating the expression of genes essential to numerous cellular processes. While it is well established that Myc functions by binding to its target genes to regulate their transcription, the distribution of the transcriptional output across human genome in Myc-amplified cancer cells, and the susceptibility of such transcriptional outputs to therapeutic interferences remain to be fully elucidated. Here, we analyze the distribution of transcriptional outputs in Myc-amplified medulloblastoma (MB) cells by profiling nascent total RNAs within a temporal context. This profiling reveals a major portion of transcriptional action in these cells was directed at the genes fundamental to cellular infrastructures, including rRNAs and particularly those in the mitochondrial genome (mtDNA). Notably, even when Myc protein was depleted by as much as 80%, the impact on transcriptional outputs across the genome was limited, with notable reduction mostly in genes of involved in ribosomal biosynthesis, genes residing in mtDNA or encoding mitochondria-localized proteins, and those encoding histones. In contrast to the limited direct impact of Myc depletion, we found that the global transcriptional outputs were highly dependent on the activity of Inosine Monophosphate Dehydrogenases (IMPDHs), rate limiting enzymes for de novo guanine nucleotide synthesis and whose expression in tumor cells was positively correlated with Myc’s expression. Blockage of IMPDHs attenuated the global transcriptional outputs with a particularly strong inhibitory effect on the aforementioned infrastructure genes, which was accompanied by the abrogation of MB cell’s proliferation in vitro and in vivo. Together, our findings reveal a real time action of Myc as a transcriptional factor in tumor cells, gain new insight into the pathogenic mechanism underlying Myc-driven tumorigenesis, and support IMPDHs as a therapeutic vulnerability in MB cells empowered by a high level of Myc oncoprotein.

scholarly journals miRNA Clusters with Up-Regulated Expression in Colorectal Cancer

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2979
Author(s):  
Paulína Pidíková ◽  
Iveta Herichová
Keyword(s):  
Colorectal Cancer ◽  
Target Genes ◽  
Expression Patterns ◽  
Clinicopathological Characteristics ◽  
Cancer Tissue ◽  
Poor Patient ◽  
Regulated Expression ◽  
Mirna Clusters ◽  
Non Coding Rnas ◽  
Poor Patient Survival

Colorectal cancer (CRC) is one of the most common malignancies in Europe and North America. Early diagnosis is a key feature of efficient CRC treatment. As miRNAs can be used as CRC biomarkers, the aim of the present study was to analyse experimentally validated data on frequently up-regulated miRNA clusters in CRC tissue and investigate their members with respect to clinicopathological characteristics of patients. Based on available data, 15 up-regulated clusters, miR-106a/363, miR-106b/93/25, miR-17/92a-1, miR-181a-1/181b-1, miR-181a-2/181b-2, miR-181c/181d, miR-183/96/182, miR-191/425, miR-200c/141, miR-203a/203b, miR-222/221, mir-23a/27a/24-2, mir-29b-1/29a, mir-301b/130b and mir-452/224, were selected. The positions of such clusters in the genome can be intronic or intergenic. Most clusters are regulated by several transcription factors, and miRNAs are also sponged by specific long non-coding RNAs. In some cases, co-expression of miRNA with other cluster members or host gene has been proven. miRNA expression patterns in cancer tissue, blood and faeces were compared. Based on experimental evidence, 181 target genes of selected clusters were identified. Panther analysis was used to reveal the functions of the target genes and their corresponding pathways. Clusters miR-17/92a-1, miR-106a/363, miR-106b/93/25 and miR-183/96/182 showed the strongest association with metastasis occurrence and poor patient survival, implicating them as the most promising targets of translational research.

scholarly journals Loss of RBMS1 as a regulatory target of miR-106b influences cell growth, gap closing and colony forming in prostate carcinoma

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Jaroslaw Thomas Dankert ◽  
Marc Wiesehöfer ◽  
Sven Wach ◽  
Elena Dilâra Czyrnik ◽  
Gunther Wennemuth
Keyword(s):  
Prostate Carcinoma ◽  
Target Genes ◽  
Rna Binding ◽  
Regulate Gene Expression ◽  
Tumour Development ◽  
Differentially Expressed Mirna ◽  
Non Coding Rnas ◽  
The Impact ◽  
First Time ◽  
Gap Closing

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.

Abstract 13650: Microrna Signatures in the Transition From Left Ventricular Hypertrophy to Cardiac Dysfunction

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Melissa Swinnen ◽  
Hadewich Hermans ◽  
Mattia Quattrocelli ◽  
Peter Pokreisz ◽  
Hilde Gillijns ◽  
...  
Keyword(s):  
Left Ventricular Hypertrophy ◽  
Cardiac Dysfunction ◽  
Ventricular Hypertrophy ◽  
Expression Patterns ◽  
Left Ventricular ◽  
Luciferase Assay ◽  
Compensatory Response ◽  
Lv Dysfunction ◽  
The Impact

Purpose: Left ventricular hypertrophy (LVH) is not just a compensatory response to increased biomechanical stress but is often associated with unfavorable outcome in patients. Mechanisms that govern transition from subclinical LVH to LV dysfunction are incompletely understood. Lately, single microRNAs (miRs), a class of small non-coding RNAs, have been implicated in LVH, but the expression dynamics and their role in transition to LV dysfunction remain unknown. Methods: We subjected mice to transverse aortic constriction (TAC) for 2, 4 and 10 weeks(wks) or to Ang-2 infusion for 4wks. Cardiac function was examined using serial echocardiography (TTE) and compared to sham mice (SH). MiR profiles in LV tissue were studied using the Nanostring platform, with significant differences between TAC or Ang2 vs SH set at a >2 up-or down-regulation with p<0.01. Western blotting and luciferase assay were performed for target confirmation. The impact of up-regulated miRs was validated in vivo by administration of specific AntagomiR vs Scrambled miRs (SCR) after TAC. Results-TTE showed a modest increase in LV end-systolic dimensions and a decline in fractional shortening (FS) after 4wks TAC and Ang2 . However, after 10wks TAC, LV dilation was present together with a reduction in FS (table1). Cardiac miR signatures indicated that 3 miRs were selectively up-regulated when transition to LV dysfunction was present at 10wks TAC. A common target gene for 2 of these up-regulated miRs (miR764-3p and miR-130b-3p) was confirmed. Moreover, in vivo antagomiR treatment for both miRs protected against cardiac dysfunction and fibrosis(table 1). Conclusion: miR analyses show important time- and stressor-dependent dynamic expression patterns during pressure overload. The miR signatures associated with transition from LVH to LV dysfunction and subsequent targeted antagomiR administration may hold promise for future therapy.

scholarly journals Overexpression of miR-1306-5p, miR-3195, and miR-3914 Inhibits Ameloblast Differentiation through Suppression of Genes Associated with Human Amelogenesis Imperfecta

2021 ◽  
Vol 22 (4) ◽  
pp. 2202
Author(s):  
Hiroki Yoshioka ◽  
Yin-Ying Wang ◽  
Akiko Suzuki ◽  
Meysam Shayegh ◽  
Mona V. Gajera ◽  
...  
Keyword(s):  
Potential Role ◽  
Target Genes ◽  
Expression Patterns ◽  
Mirna Gene ◽  
Amelogenesis Imperfecta ◽  
Transcriptional Level ◽  
Specific Expression ◽  
Protein Protein Interaction ◽  
Bioinformatic Tools ◽  
Non Coding Rnas

Amelogenesis imperfecta is a congenital form of enamel hypoplasia. Although a number of genetic mutations have been reported in humans, the regulatory network of these genes remains mostly unclear. To identify signatures of biological pathways in amelogenesis imperfecta, we conducted bioinformatic analyses on genes associated with the condition in humans. Through an extensive search of the main biomedical databases, we found 56 genes in which mutations and/or association/linkage were reported in individuals with amelogenesis imperfecta. These candidate genes were further grouped by function, pathway, protein–protein interaction, and tissue-specific expression patterns using various bioinformatic tools. The bioinformatic analyses highlighted a group of genes essential for extracellular matrix formation. Furthermore, advanced bioinformatic analyses for microRNAs (miRNAs), which are short non-coding RNAs that suppress target genes at the post-transcriptional level, predicted 37 candidates that may be involved in amelogenesis imperfecta. To validate the miRNA–gene regulation association, we analyzed the target gene expression of the top seven candidate miRNAs: miR-3195, miR-382-5p, miR-1306-5p, miR-4683, miR-6716-3p, miR-3914, and miR-3935. Among them, miR-1306-5p, miR-3195, and miR-3914 were confirmed to regulate ameloblast differentiation through the regulation of genes associated with amelogenesis imperfecta in AM-1 cells, a human ameloblastoma cell line. Taken together, our study suggests a potential role for miRNAs in amelogenesis imperfecta.

scholarly journals Role of MicroRNAs and Long Non-Coding RNAs in Sarcopenia

Cells ◽  
2022 ◽  
Vol 11 (2) ◽  
pp. 187
Author(s):  
Jihui Lee ◽  
Hara Kang
Keyword(s):  
Skeletal Muscle ◽  
Signaling Pathways ◽  
Molecular Mechanisms ◽  
Expression Patterns ◽  
Treatment Strategies ◽  
The Elderly ◽  
Muscle Physiology ◽  
Age Related ◽  
Non Coding Rnas ◽  
The Impact

Sarcopenia is an age-related pathological process characterized by loss of muscle mass and function, which consequently affects the quality of life of the elderly. There is growing evidence that non-coding RNAs, including microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), play a key role in skeletal muscle physiology. Alterations in the expression levels of miRNAs and lncRNAs contribute to muscle atrophy and sarcopenia by regulating various signaling pathways. This review summarizes the recent findings regarding non-coding RNAs associated with sarcopenia and provides an overview of sarcopenia pathogenesis promoted by multiple non-coding RNA-mediated signaling pathways. In addition, we discuss the impact of exercise on the expression patterns of non-coding RNAs involved in sarcopenia. Identifying non-coding RNAs associated with sarcopenia and understanding the molecular mechanisms that regulate skeletal muscle dysfunction during aging will provide new insights to develop potential treatment strategies.

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