Combinatorial analysis of miRNA and mRNA expression in pancreatic ductal adenocarcinoma (PDAC)_mRNA
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE41368 | GEO | 2013/12/30
SECONDARY ACCESSION(S): PRJNA176698
REPOSITORIES: GEO
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Project description:miRNAs are known to be involved in PDAC tumorigenesis, but only a few biologically relevant gene targets have been identified. Here we show that three miRNAs (miR-21, miR-23a and miR-27a) act in concert for the cooperative suppression of several tumor suppressor genes of which we experimentally validated PDCD4, BTG2 and NEDD4L. The synergistic inhibition of this triple miRNA combination is capable of reducing PDAC growth in a mouse model greater than inhibition of oncomiR-21 alone.
2013-12-30 | GSE41369 | GEO
Project description:miRNAs are known to be involved in PDAC tumorigenesis, but only a few biologically relevant gene targets have been identified. Here we show that three miRNAs (miR-21, miR-23a and miR-27a) act in concert for the cooperative suppression of several tumor suppressor genes of which we experimentally validated PDCD4, BTG2 and NEDD4L. The synergistic inhibition of this triple miRNA combination is capable of reducing PDAC growth in a mouse model greater than inhibition of oncomiR-21 alone. Patients samples of normal pancreas (n=6) or pancreatic ductal adenocarcinoma (PDAC; n=6) were retrieved during surgery and placed in RNA Later stabilization fluid and then kept at minus 80 until required.
2013-12-30 | E-GEOD-41368 | biostudies-arrayexpress
Project description:miRNAs are known to be involved in PDAC tumorigenesis, but only a few biologically relevant gene targets have been identified. Here we show that three miRNAs (miR-21, miR-23a and miR-27a) act in concert for the cooperative suppression of several tumor suppressor genes of which we experimentally validated PDCD4, BTG2 and NEDD4L. The synergistic inhibition of this triple miRNA combination is capable of reducing PDAC growth in a mouse model greater than inhibition of oncomiR-21 alone. Patients samples of normal pancreas (n=9) or pancreatic ductal adenocarcinoma (PDAC; n=9) were retrieved during surgery and placed in RNA Later stabilization fluid and then kept at minus 80 until required.
2013-12-30 | E-GEOD-41369 | biostudies-arrayexpress
Project description:The miR-23a-27a-24-2 cluster is overexpressed in human cancers, including hepatocellular carcinoma (HCC). However, the role of three mature miRNAs of the miR-23a-27a-24-2 cluster in HCC is still controversial. Also, the integrative role of the miR-23a-27a-24-2 cluster in HCC remains elusive. In the present study, using CRISPR knockout (KO), CRISPR interference (CRISPRi), and CRISPR activation (CRISPRa) technologies, we established an endogenous miR-23a-27a-24-2 controllable and various knockout (KO) cell models, which were used to dissect the functional role and underlying signaling of the miR-23a-27a-24-2 cluster. Either miR-23a KO or miR-27a KO reduced cell growth in vitro and in vivo. Of particular note, endogenous miRNAs in the miR-23a-27a-24-2 cluster were effectively regulated by CRISPRi/a, identifying an integrated oncogenic role of the miR-23a-27a-24-2 cluster in HCC cells. Functional analysis showed that miR-23a KO and miR-27a KO led the cell cycle arrest, especially at the G2/M phase, by reducing CDK1/cyclin B activation in HCC cells. Furthermore, a high-throughput RNA-seq approach with miRNA target prediction identified the miR-23a/miR-27a-regulated gene network, further validated by various technologies. In addition, miR-23a and miR-27a have opposite roles in cell migration and mesenchymal-epithelial transition. However, an integrated analysis by CRISPRi/a suggested an oncogenic role of the miR-23a-27a-24-2 cluster in cell migration, which may require a miR-23a-BMPR2-Smad-Snail axis in HCC cells. Thus, our CRISPRi/a study offers a valuable research tool for dissecting the integrated role and underlying mechanism of an endogenous miRNA cluster. Also, this CRISPR approach may provide new routes of miRNA intervention for miRNA targeted therapy.
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Project description:The Epstein-Barr virus (EBV) is associated with lymphoid and epithelial cancers. Initial EBV infection alters lymphocyte gene expression, inducing cellular proliferation and differentiation as the virus transitions through consecutive latency transcription programs. Cellular microRNAs (miRNAs) are important regulators of signaling pathways and are implicated in carcinogenesis. The extent to which EBV exploits cellular miRNAs is unknown. Using micro-array analysis and quantitative PCR, we demonstrate differential expression of cellular miRNAs in type III versus type I EBV latency including elevated expression of miR-21, miR-23a, miR-24, miR-27a, miR-34a, miR-146a and b, and miR-155. In contrast, miR-28 expression was found to be lower in type III latency. The EBV-mediated regulation of cellular miRNAs may contribute to EBV signaling and associated cancers.
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2015-02-12 | E-GEOD-65874 | biostudies-arrayexpress
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2023-06-14 | GSE232714 | GEO
Project description:Purpose: miRNAs, a member of the small RNA, play critical roles in the mammalian spermatogenesis. Spermatogonia was the foundation of spermatogenesis and valuable for the study of spermatogenesis. However, it is still not clear that the expression profiling of the miRNAs in spermatogonia of dairy goat. Methods: The CD49f was one of the surface markers for spermatogonia enrichment by MACS. Therefore, we used CD49f microbeads antibody to purify CD49f-positive and negative cells of dairy goat testicular cells by MACS (Magnetic Activated Cell Sorting), and then in-depth analyzed the miRNA expression in these cells using Illumina sequencing technology. Results: The results of miRNAs expression profiling in purified CD49f-positive and negative testicular cells showed that 933 were miRNAs upregulated in CD49f-positive cells and 916 were miRNAs upregulated in CD49f-negative cells with a 2-fold increase, respectively; some spermatogonial stem cells(SSCs) specific miRNAs and marker genes in testis had a higher level expression in CD49f-positive testicular cells, such as miR-221, miR-23a, miR-29b, miR-24, miR-29a, miR-199b, miR-199a, miR-27a, miR-21. Conclusions: our comparative miRNAome data provided some useful miRNAs profiling data of dairy goat spermatogonia cells and suggested CD49f could be used to enrich dairy goat spermatogonia-like cells, including SSCs.
2014-04-25 | GSE57041 | GEO
Project description:Purpose: miRNAs, a member of the small RNA, play critical roles in the mammalian spermatogenesis. Spermatogonia was the foundation of spermatogenesis and valuable for the study of spermatogenesis. However, it is still not clear that the expression profiling of the miRNAs in spermatogonia of dairy goat. Methods: The CD49f was one of the surface markers for spermatogonia enrichment by MACS. Therefore, we used CD49f microbeads antibody to purify CD49f-positive and negative cells of dairy goat testicular cells by MACS (Magnetic Activated Cell Sorting), and then in-depth analyzed the miRNA expression in these cells using Illumina sequencing technology. Results: The results of miRNAs expression profiling in purified CD49f-positive and negative testicular cells showed that 933 were miRNAs upregulated in CD49f-positive cells and 916 were miRNAs upregulated in CD49f-negative cells with a 2-fold increase, respectively; some spermatogonial stem cells(SSCs) specific miRNAs and marker genes in testis had a higher level expression in CD49f-positive testicular cells, such as miR-221, miR-23a, miR-29b, miR-24, miR-29a, miR-199b, miR-199a, miR-27a, miR-21. Conclusions: our comparative miRNAome data provided some useful miRNAs profiling data of dairy goat spermatogonia cells and suggested CD49f could be used to enrich dairy goat spermatogonia-like cells, including SSCs. miRNA profiles of goat CD49f-positive and negative testicular cells were generated by deep sequencing, in triplicate, using Illumina GAIIx
2014-04-25 | E-GEOD-57041 | biostudies-arrayexpress
Project description:Solexa/Illumina deep sequencing was used to obtain miRNA transcriptome profiles for control (basal diet, 14.49% crude protein, 13.73 MJ/kg digestible energy, 0.86% available lysine) and traditional Chinese medicine formula (basal diet+2.5 g/kg traditional Chinese medicine formula) groups. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis was performed using DAVID functional annotation to identify the biological process function of the miRNAs identified as being involved in muscle fiber regulation. We detected 269 mature miRNAs and 14 pre-miRNAs in the porcine muscle samples, of which 211 were previously unreported. Pathway analyses suggested that several independent signaling pathways were involved in the biological process, cellular component, and molecular function categories, with metabolic pathways showing the most enrichment and including some pathways involved in the regulation of muscle fiber phenotype such as mitogen-activated protein kinase (MAPK), mammalian target of rapamycin, and citrate cycle signaling pathways. Thirty-seven miRNAs exhibited normalized expression of over 10,000 reads per million, accounting for 85.91% of the overall counts of the total porcine mature miRNAs. Among these, 9 were muscle-related miRNAs involved in muscle development, including skeletal satellite cell (ssc)-miR-133a-3p, ssc-miR-486, ssc-miR-26a, ssc-miR-21, ssc-miR-1, ssc-miR-10b, ssc-miR-181a, ssc-miR-128, and ssc-miR-23a. In particular, miR-1 and miR-133 are muscle-specific miRNAs, termed myomiRs, which play an important role in muscle differentiation and development. Furthermore, porcine skeletal satellite cell transfection experiments indicated that overexpression or inhibition of ssc-miR-27a repressed or increased, respectively, MYH7 gene and protein expression through the PGC-1-MEF2C pathway, suggesting that miR-27a participated in the regulation of muscle fiber in skeletal muscle. In conclusion, these miRNAome profiles provide novel insight into the mechanism underlying muscle fiber regulation.
2017-04-07 | GSE80069 | GEO