Grape Proanthocyanidins Modulate MicroRNA Expression in Human pancreatic cancer cells
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE107409 | GEO | 2019/03/20
REPOSITORIES: GEO
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Project description:In this study, we selected differentially expressed miRNAs through construcing and analyzing the miRNA expression profile during 2-, 6-, and 12- month-old Small Tail Han Sheep ovaries, which provided a theoretical basis for the study of miRNAs regulating the reproduction of Small Tail Han Sheep. RNASeq techniques were used to perform profile analysis for these ovaries. The results showed that 11, 13 and 19 DE miRNAs were identified in 2- vs 6-, 6- vs 12-, and 2- vs 12-month-old ovaries, respectively. In total, 54, 37, and 198 predicted target genes of DE miRNAs were obtained from these three groups, respectively. GO and KEGG analyses showed that, in 2- vs 6-month-olds, the target genes of DE known sheep miRNAs were involved in 102 GO terms and 7 signaling pathways; in 6- vs 12-month-olds, the target genes of DE known sheep miRNAs were involved in 52 GO terms and 3 signaling pathways; and in 2- vs 12-month-olds, the target genes of DE known sheep miRNAs were involved in 88 GO terms and 6 signaling pathways. Three miR–target regulatory networks were constructed based on these DE miRNA–targets. 9 miRNAs were selected to validate the accuracy of miRNA sequencing data by qRT-PCR. The binding sites of oar-miR-432 with RPS6KA1 was validated by a dual luciferase reporter gene detection system. This is the first integrative analysis of miRNA and mRNA expression profiles in Small Tail Han Sheep ovarian development. These data help elucidate the molecular regulatory mechanisms in sheep ovarian development and identify the biomarkers that influence reproductive performance of Small Tail Han Sheep ewe.
2018-11-16 | GSE122607 | GEO
Project description:MicroRNAs (miRNAs) play a important part in post-transcriptional gene regulation and have been shown to control many genes involved in various biological and metabolic processes. There have been extensive studies to discover miRNAs and analyze their functions in model plant species, such as Arabidopsis and rice and other plants. However, the number of miRNAs discovered in grape is relatively low and little is known about miRNAs responded gibberellin during fruit germination. In this study, a small RNA library from gibberellin grape fruits was sequenced by the high throughput sequencing technology. A total of 16,033,273 reads were obtained. 812,099 total reads representing 1726 unique sRNAs matched to known grape miRNAs. Further analysis confirmed a total of 149 conserved grapevine miRNA (Vv-miRNA) belonging to 27 Vv-miRNA families were validated, and 74 novel potential grapevine-specific miRNAs and 23 corresponding novel miRNAs* were discovered. Twenty-seven (36.5%) of the novel miRNAs exhibited differential QRT-PCR expression profiles in different development gibberellin-treated grapevine berries that could further confirm their existence in grapevine. QRT-PCR analysis on transcript abundance of 27 conserved miRNA family and the new candidate miRNAs revealed that most of them were differentially regulated by the gibberellin, with most conserved miRNA family and 26 miRNAs being specifically induced by gibberellin exposure. All novel sequences had not been earlier described in other plant species. In addition, 117 target genes for 29 novel miRNAs were successfully predicted. Our results indicated that miRNA-mediated gene expression regulation is present in gibberellin-treated grape berries. This study led to the confirmation of 101 known miRNAs and the discovery of 74 novel miRNAs in grapevine. Identification of miRNAs resulted in significant enrichment of the gibberellin of grapevine miRNAs and provided insights into miRNA regulation of genes expressed in grape berries. GSM604831 is the control for the gibberellin-treated sample.
2013-10-05 | GSE39734 | GEO
Project description:MicroRNAs (miRNAs) play a important part in post-transcriptional gene regulation and have been shown to control many genes involved in various biological and metabolic processes. There have been extensive studies to discover miRNAs and analyze their functions in model plant species, such as Arabidopsis and rice and other plants. However, the number of miRNAs discovered in grape is relatively low and little is known about miRNAs responded gibberellin during fruit germination. In this study, a small RNA library from gibberellin grape fruits was sequenced by the high throughput sequencing technology. A total of 16,033,273 reads were obtained. 812,099 total reads representing 1726 unique sRNAs matched to known grape miRNAs. Further analysis confirmed a total of 149 conserved grapevine miRNA (Vv-miRNA) belonging to 27 Vv-miRNA families were validated, and 74 novel potential grapevine-specific miRNAs and 23 corresponding novel miRNAs* were discovered. Twenty-seven (36.5%) of the novel miRNAs exhibited differential QRT-PCR expression profiles in different development gibberellin-treated grapevine berries that could further confirm their existence in grapevine. QRT-PCR analysis on transcript abundance of 27 conserved miRNA family and the new candidate miRNAs revealed that most of them were differentially regulated by the gibberellin, with most conserved miRNA family and 26 miRNAs being specifically induced by gibberellin exposure. All novel sequences had not been earlier described in other plant species. In addition, 117 target genes for 29 novel miRNAs were successfully predicted. Our results indicated that miRNA-mediated gene expression regulation is present in gibberellin-treated grape berries. This study led to the confirmation of 101 known miRNAs and the discovery of 74 novel miRNAs in grapevine. Identification of miRNAs resulted in significant enrichment of the gibberellin of grapevine miRNAs and provided insights into miRNA regulation of genes expressed in grape berries. GSM604831 is the control for the gibberellin-treated sample. The mixture samples of young berries (one week after flowering) large berries (five week after flowering after flowering), and old berries (nine week after flowering) treated with gibberellin, respectively, were generated by deep sequencing, in triplicate, using Illumina 1G Genome Analyzer.
2013-10-05 | E-GEOD-39734 | biostudies-arrayexpress
Project description:To elucidate the complex physiological process of testis development and spermatogenesis in Sika deer, this study evaluated the changes of miRNA profiles in the four developmental stages of testis the juvenile (1-year-old), adolescence (3-year-old), adult (5-year-old) and aged (10-year-old) stages. The results showed that total total of 198 mature and 66 novel miRNAs were obtained. 88 (43 up and 45 down), 102 (44 up and 58 down), 54 (18 up and 36 down) DE miRNAs were identified in 3-vs.1-, 5-vs.3- and 10-vs.5-year-old testes, respectively. By integrating miRNA expression profiles, we predicted 69883 miRNA-mRNA interaction sites. The target genes were enriched by GO and KEGG pathways to obtain DE miRNA (miR-145, miR-140, miR-7, miR-26a, etc.), which play an important role in testis development and spermatogenesis. The data show that DE miRNAs could regulate testis developmental and spermatogenesis through signaling pathways, including MAPK signaling pathway, p53 signaling pathway, PI3K-Akt signaling pathway, Hippo signaling pathway, etc. It provides a useful resource for future studies on the role of miRNA regulation in testis development and spermatogenesis.
2021-11-10 | GSE188369 | GEO
Project description:The semen of Small Tail Han Sheep has characteristics of high yield, high density, and good motility. To reveal the key miRNAs, mRNAs and miR-Targets regulatory mechanisms in Small Tail Han Sheep testes development, integrated analysis of miRNA and mRNA expression profiles in 2-, 6-, and 12-month-old testes were investigated by RNA-seq technology and bioinformatics methods. As the results shown: 630, 102, and 322 differentially expressed (DE) mRNAs; 5, 1 and 4 DE known miRNAs; 132, 105 and 24 DE novel miRNAs were identified in 2- vs 6-month-old, 6- vs 12-month-old, and 2- vs 12-month-old testes, respectively. GO and pathway analysis showed: in 2- vs 6-month-old testes, DE mRNAs were mainly involved in sexual maturation process and the DE mRNAs were mainly involved in multiple metabolism and biosynthesis pathways; in 6- vs 12-month-old testes, DE mRNAs were mainly involved in metabolism and translation processes, and the most significant pathway that DE mRNAs involved in was ribosome pathway; in 2- vs 12-month-old testes, DE mRNAs were mainly involved in metabolism and physiological processes, and DE mRNAs were mainly involved in multiple metabolism and biosynthesis pathways. Subsequently, 76, 11 and 1 DE miR-Targets were identified in 2- vs 6-month-old, 2- vs 12-month-old, and 6- vs 12-month-old testes, respectively. 3 miR-Target regulatory networks were constructed based on these miR-Targets, which helped to elucidate the regulatory metabolism in Small Tail sheep testes development. Finally, 6 miRNAs and 7 mRNAs were selected to validate the RNA-seq data by RT-PCR.
2017-12-10 | GSE107803 | GEO
Project description:Hypoxia negatively affects the behavior, growth, reproduction, and survival of fish, causing serious economic losses to aquaculture. Rainbow trout (Oncorhynchus mykiss), an important economic fish worldwide, belongs to a hypoxia-sensitive fish species. However, the regulatory mechanisms of miRNAs under hypoxia stress response of rainbow trout remains unclear. In this study, rainbow trout were subjected to hypoxia stress (DO: 3.5 mg/L) for 3 h (H3h_L), 12 h (H12h_L), 24 h (H24h_L) and 3 h reoxygenation (R3h_L) to systemically evaluate the changes of miRNA expression profiles in liver, and the functions of sha-miR-92a_L+2R+4 were investigated. We found 17, 144, 57 and 55 differentially expressed (DE) miRNAs in H3h_L vs. control (N_L), H12h_L vs. N_L, H24h_L vs. N_L and R3h_L vs. N_L comparisons, respectively. Enrichment analysis revealed that the targets of these DE miRNAs were significantly enriched in HIF signaling pathway, VEGF signaling pathway, FoxO signaling pathway and glycolysis/gluconeogenesis. Through miRNA-mRNA nteraction and weighted gene co-expression network analysis (WGCNA), five key DE miRNAs (sha-miR-92a_L+2R+4, ssa-miR-128-3p, ssa-miR-101b-3p_R+1, ola-miR-199a-5p_R+2 and tni-miR-199_1ss18CG) were identified, which can target at least two hypoxia-responsive genes, such as vegfaa, ho, glut1a and junb. Functional analysis found that sha-miR-92a_L+2R+4 directly regulated vegfaa expression by targeting its 3′-UTR, overexpression of sha-miR-92a_L+2R+4 significantly decreased vegfaa expression in rainbow trout liver cells, while opposite results were obtained after transfection of sha-miR-92a_L+2R+4 inhibitor. Furthermore, overexpression of sha-miR-92a_L+2R+4 promoted rainbow trout liver cell proliferation and inhibited apoptosis. These results deepen our understanding of the crucial roles of miRNAs under hypoxia stress in rainbow trout, and provide valuable information for further studying the regulatory mechanisms of key hypoxia-responsive miRNAs and breeding hypoxia-tolerant rainbow trout species.
2023-05-10 | GSE231752 | GEO
Project description:Clear cell renal cell carcinomas (ccRCC) are characterized by arm-wide chromosomal alterations. Loss at 14q is associated with disease aggressiveness in ccRCC, which responds poorly to chemotherapeutics. The 14q locus contains one of the largest miRNA clusters in the human genome; however, little is known about the contribution of these miRNAs to ccRCC pathogenesis. In this regard, we investigated the expression pattern of selected miRNAs at the 14q32 locus in TCGA kidney tumors and in ccRCC cell lines. We validated that the miRNA cluster is downregulated in ccRCC (and cell lines) as well as in papillary kidney tumors relative to normal kidney tissues and primary renal proximal tubule epithelial (RPTEC) cells. We demonstrated that agents modulating expression of DNMT1 (e.g., 5-Aza-deoxycytidine) could modulate miRNA expression in ccRCC cell lines. Lysophosphatidic acid (LPA, a Lysophospholipid mediator elevated in ccRCC) not only increased labile iron content but also modulated expression of 14q32 miRNAs. Through an overexpression approach targeting a subset of 14q32 miRNAs (specifically at subcluster A: miR-431, miR-432, miR-127, and miR-433) in 769-P cells, we uncovered changes in cellular viability and claudin-1, a tight junction marker. A global proteomic approach was implemented using these miRNA overexpressing cell lines which uncovered ATXN2 as a highly downregulated target, which has a role in chronic kidney disease pathogenesis. Collectively, these findings support a contribution of miRNAs at 14q32 in ccRCC pathogenesis.
2023-05-10 | PXD036428 | Pride
Project description:Mi(cro)RNAs are small non-coding RNAs of 18-25 nucleotides in length that modulate gene expression at the post-transcriptional level. These RNAs have been shown to be involved in a several biological processes, human diseases and metabolic disorders. Proanthocyanidins, which are the most abundant polyphenol class in the human diet, have positive heath effects on a variety of metabolic disorders such as inflammation, obesity, diabetes and insulin resistance. The present study aimed to evaluate whether proanthocyanidin-rich natural extracts modulate miRNA expression. Using microarray analysis and Q-PCR, we investigated miRNA expression in HepG2 cells treated with proanthocyanidins. Our results showed that when HepG2 cells were treated with grape seed proanthocyanidin extract (GSPE), cocoa proanthocyanidin extract (CPE) or pure epigallocatechin gallate isolated from green tea (EGCG), fifteen, six and five differentially expressed miRNAs, respectively, were identified out of 904 mRNAs. Specifically, miR-30b* was downregulated by the three treatments, and treatment with GSPE or CPE upregulated miR-1224-3p, miR-197 and miR-532-3p. Therefore, these results provide evidence of the capacity of dietary proanthocyanidins to influence microRNA expression, revealing a new mechanism of action of proanthocyanidins. microRNA profiling of Human hepatocellular liver carcinoma cell line (HepG2) comparing control untreated HepG2 cells with cells treated with grape seed proanthocyanidin extract (100 mg/L, 5h), cacao proanthocyanidin extract (100 mg/L, 5h) or epigallocatechin gallate (50 mg/L, 5h). Two biologival replicates were used for control and treated cells with one replicate per array.
2014-07-01 | E-GEOD-30575 | biostudies-arrayexpress
Project description:DEAD-box RNA-binding proteins (RBPs) play a significant role in RNA metabolism to achieve cellular homeostasis, including miRNA biogenesis and transcription. Hypoxia induces stemness cell-like characteristics in cancer cells and promotes malignant progression. Despite the fact that hypoxia can induce the changes in protein and RNA modification, thereby regulating downstream gene expressions, how modifications at different molecular layers interplay with each other are poorly understood. Here we show that hypoxia induces HectH9-mediated K63-linked polyubiquitination of the DEAD-box protein DDX17 as well as reduces N6-methyladenosine (m6A) marks in pri-miRNAs. While m6A potentiates DDX17 binding to pri-miRNAs, decreased m6A modifications of pri-miRNAs and increased polyubiquitination of DDX17 under hypoxia lead to decreased DDX17 binding to pri-miRNAs binding. These events enhance the association of DDX17 with the ubiquitin receptor p300 and lead to a decrease in miRNA biogenesis, especially for miRNAs regulating stemness and stemness-related genes. In addition, polyubiquitinated DDX17 together with p300 upregulates H3K56Ac levels on the stemness and stemness-related genes, resulting in enhancement of tumor initiating ability. Post-transcriptionally, decreased miRNA production, including those targeting stemness genes or stemness-related genes, also facilitates tumor initiation. Together, hypoxia triggers DDX17 poly-ubiquitination, which orchestrates dual mechanisms to increase tumor initiating ability and promote tumor progression.
2018-03-09 | PXD006059 | JPOST Repository
Project description:Objective: The expression pattern of exosomal miRNAs derived from parathyroid tumor is still unknown. In the present work, we aimed to examine the differences on microRNA (miRNA) expression, present in serum exosomes, by comparing parathyroid carcinoma (PC) and parathyroid adenoma (PA). Methods: MiRNA expression profile of serum exosomes, derived from 4 PC patients and 4 PA patients, were analyzed by next-generation sequencing technology. The differential expressions of target miRNAs were further verified in both serum exosomes and tissues of PC/PA patients by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Lastly, receiver operating characteristic (ROC) curves were plotted to investigate the efficiency of target exosomal miRNAs in distinguishing PC patients from PA controls. Results: Multiple differentially expressed miRNAs of serum exosomes were screened out by sequencing. Based on this screening, hsa-miR-146b-5p (p=0.0846), hsa-miR-27a-5p (p=0.0412), hsa-miR-93-5p (p=0.73), hsa-miR-381-3p (p=0.1239) and hsa-miR-134-5p (p=0.0694) were up-regulated in the serum exosomes of PC patients. These results were validated by qPCR, where the trend on differential miRNA expression was consistent with the sequencing results. Specifically, the expression of exosomal hsa-miR-27a-5p was able to clearly distinguish PC patients from PA controls, and related analysis indicated that the area under the ROC curve was 0.8594 (p=0.0157). Conclusion: Here we present, for the first time, the miRNA expression profile of serum exosomes derived from PC patients. Based on this result, we presently suggest that the exosomal hsa-miR-27a-5p may serve as a putative tumor marker for preoperative identification of PC and PA subjects.
2020-11-13 | GSE161339 | GEO