Improved lung cancer classification by employing diverse molecular features of microRNAs
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE244311 | GEO | 2024/02/22
REPOSITORIES: GEO
Similar Datasets
Project description:Background: Adenosine deaminases that act on RNA (ADARs) bind to double-stranded and structured RNAs and deaminate adenosines to inosines. This A to I editing is widespread and required for normal life and development. Besides mRNAs and repetitive elements, ADARs can target miRNA precursors. Editing of miRNA precursors can affect processing efficiency and alter target specificity. Interestingly, ADARs can also influence miRNA abundance independent of RNA-editing. In mouse embryos where editing levels are low, ADAR2 was found to be the major ADAR protein that affects miRNA abundance. Here we extend our analysis to adult mouse brains where high editing levels are observed. Results: Using Illumina deep sequencing we compare the abundances of mature miRNAs and editing events within them, between wild-type and ADAR2 knockout mice in the adult mouse brain. Reproducible changes in abundance of specific miRNAs are observed in ADAR2 deficient mice. Most of these quantitative changes seem unrelated to A to I editing events. However, many A to G transitions in cDNAs prepared from mature miRNA sequences, reflecting A to I editing events in the RNA, are observed with frequencies reaching up to 80%. About half of these editing events are primarily caused by ADAR2 while a few miRNAs show increased editing in the absence of ADAR2, suggesting preferential editing by ADAR1. Moreover, novel, previously unknown editing events were identified in several miRNAs. In general 64% of all editing events are located within the seed region of mature miRNAs. In one of these cases retargeting of the edited miRNA could be verified in reporter assays. Also, altered processing efficiency upon editing near a processing site could be experimentally verified. Conclusions: ADAR2 can significantly influence the abundance of certain miRNAs in the brain. Only in a few cases changes in miRNA abundance can be explained by miRNA editing. Thus, ADAR2 binding to miRNA precursors, without editing them, may influence their processing and thereby abundance. ADAR1 and ADAR2 have both overlapping and distinct specificities for editing of miRNA editing sites. Over 60% of editing occurs in the seed region possibly changing target specificities for many edited miRNAs. Examination of the effect of ADAR2 on mature miRNA abundance and sequence in adult mouse brain.
2014-10-02 | E-GEOD-61066 | biostudies-arrayexpress
Project description:Background: Adenosine deaminases that act on RNA (ADARs) bind to double-stranded and structured RNAs and deaminate adenosines to inosines. This A to I editing is widespread and required for normal life and development. Besides mRNAs and repetitive elements, ADARs can target miRNA precursors. Editing of miRNA precursors can affect processing efficiency and alter target specificity. Interestingly, ADARs can also influence miRNA abundance independent of RNA-editing. In mouse embryos where editing levels are low, ADAR2 was found to be the major ADAR protein that affects miRNA abundance. Here we extend our analysis to adult mouse brains where high editing levels are observed. Results: Using Illumina deep sequencing we compare the abundances of mature miRNAs and editing events within them, between wild-type and ADAR2 knockout mice in the adult mouse brain. Reproducible changes in abundance of specific miRNAs are observed in ADAR2 deficient mice. Most of these quantitative changes seem unrelated to A to I editing events. However, many A to G transitions in cDNAs prepared from mature miRNA sequences, reflecting A to I editing events in the RNA, are observed with frequencies reaching up to 80%. About half of these editing events are primarily caused by ADAR2 while a few miRNAs show increased editing in the absence of ADAR2, suggesting preferential editing by ADAR1. Moreover, novel, previously unknown editing events were identified in several miRNAs. In general 64% of all editing events are located within the seed region of mature miRNAs. In one of these cases retargeting of the edited miRNA could be verified in reporter assays. Also, altered processing efficiency upon editing near a processing site could be experimentally verified. Conclusions: ADAR2 can significantly influence the abundance of certain miRNAs in the brain. Only in a few cases changes in miRNA abundance can be explained by miRNA editing. Thus, ADAR2 binding to miRNA precursors, without editing them, may influence their processing and thereby abundance. ADAR1 and ADAR2 have both overlapping and distinct specificities for editing of miRNA editing sites. Over 60% of editing occurs in the seed region possibly changing target specificities for many edited miRNAs. Examination of the effect of ADAR2 on gene expression in mature mouse wildtype and ADAR2 knockout brain using AffymetrixM-BM-. GeneChipM-BM-. Whole Transcript (WT) Expression Arrays (Analysis by KFB Regensburg, Germany)
2014-10-02 | E-GEOD-61067 | biostudies-arrayexpress
Project description:Introduction: MicroRNAs (miRNAs) in circulation have emerged as promising biomarkers. In this study we aimed to identify a circulating miRNA signature for osteoarthritis (OA) patients. Methods: Serum samples were collected from 12 primary OA patients and 12 healthy individuals and were screened using the Agilent Human miRNA Microarray. Receiver Operating Characteristic (ROC) curves were constructed to evaluate the diagnostic performance of the deregulated miRNAs. Expression levels of selected miRNAs were validated by quantitative Real-time PCR (qRT-PCR) in all serum samples and in articular cartilage samples from OA patients (n=12) and healthy individuals (n=7). Bioinformatics analysis was used to investigate the involved pathways and target genes of the above miRNAs. Results: We identified 279 differentially expressed miRNAs in the serum of OA patients compared to healthy controls. 205 (73.5%) were up-regulated and 74 (26.5%) down-regulated. ROC analysis revealed that 77 miRNAs had area under the curve (AUC)> 0.8 and p<0.05. Bioinformatics analysis in 7 out of the 77 selected miRNAs (hsa-miR-33b-3p, hsa-miR-4284, hsa-miR-671-3p, hsa-miR-663a, hsa-miR-140-3p, hsa-miR-150-5p and hsa-miR-1233-3p) revealed that their target genes were involved in multiple signaling pathways, among which FOXO, mTOR, pI3K/akt, lipid metabolism and TGF-β. A serum miRNA signature including three down-regulated miRNAs (hsa-miR-33b-3p, hsa-miR-671-3p and hsa-miR-140-3p) were also verified by qRT-PCR in OA patients. Furthermore, we found that hsa-miR-140-3p, hsa-miR-671-3p and potentially hsa-miR-33b-3p expression levels were consistently down-regulated in articular cartilage of OA patients compared to healthy individuals. Conclusions: A global miRNA serum signature was revealed in OA patients. We identified a three- miRNA signature in peripheral serum which could be potential osteoarthritis biomarkers.
2017-10-17 | GSE105027 | GEO
Project description:iPSC-derived neurons were treated with mimics and inhibitors of the miRNAs miR-150-5p, hsa-mir-193a-3p and hsa-miR-19b-3p.
RNA-sequencing was then performed to examine the effects of miRNA up-regulation and inhibition.
| EGAD00001006844 | EGA
Project description:The aim of this study was to investigate the effect of sex on miRNA expression in skeletal muscle. MiRNAs were first screened using Taqman®miRNA arrays in skeletal muscle of 42 healthy participants from the Gene SMART study (23 males and 19 females aged 18-45 yrs). Based on this 2 candidate miRNAs, hsa-miRNA-30a-5p (miR-30a) and hsa-miRNA-30c-5p (miR-30c), were overexpressed in three female and three male primary skeletal muscle lines. Overexpression of miR-30a and miR-30c was confirmed by quantifying transcript levels using qPCR RNA sequencing to understand the transcriptome profile changes driven by these miRNAs and to explore the putative biological pathways.
2023-10-05 | GSE242861 | GEO
Project description:Background: Adenosine deaminases that act on RNA (ADARs) bind to double-stranded and structured RNAs and deaminate adenosines to inosines. This A to I editing is widespread and required for normal life and development. Besides mRNAs and repetitive elements, ADARs can target miRNA precursors. Editing of miRNA precursors can affect processing efficiency and alter target specificity. Interestingly, ADARs can also influence miRNA abundance independent of RNA-editing. In mouse embryos where editing levels are low, ADAR2 was found to be the major ADAR protein that affects miRNA abundance. Here we extend our analysis to adult mouse brains where high editing levels are observed. Results: Using Illumina deep sequencing we compare the abundances of mature miRNAs and editing events within them, between wild-type and ADAR2 knockout mice in the adult mouse brain. Reproducible changes in abundance of specific miRNAs are observed in ADAR2 deficient mice. Most of these quantitative changes seem unrelated to A to I editing events. However, many A to G transitions in cDNAs prepared from mature miRNA sequences, reflecting A to I editing events in the RNA, are observed with frequencies reaching up to 80%. About half of these editing events are primarily caused by ADAR2 while a few miRNAs show increased editing in the absence of ADAR2, suggesting preferential editing by ADAR1. Moreover, novel, previously unknown editing events were identified in several miRNAs. In general 64% of all editing events are located within the seed region of mature miRNAs. In one of these cases retargeting of the edited miRNA could be verified in reporter assays. Also, altered processing efficiency upon editing near a processing site could be experimentally verified. Conclusions: ADAR2 can significantly influence the abundance of certain miRNAs in the brain. Only in a few cases changes in miRNA abundance can be explained by miRNA editing. Thus, ADAR2 binding to miRNA precursors, without editing them, may influence their processing and thereby abundance. ADAR1 and ADAR2 have both overlapping and distinct specificities for editing of miRNA editing sites. Over 60% of editing occurs in the seed region possibly changing target specificities for many edited miRNAs.
2014-10-02 | GSE61067 | GEO
Project description:Background: Adenosine deaminases that act on RNA (ADARs) bind to double-stranded and structured RNAs and deaminate adenosines to inosines. This A to I editing is widespread and required for normal life and development. Besides mRNAs and repetitive elements, ADARs can target miRNA precursors. Editing of miRNA precursors can affect processing efficiency and alter target specificity. Interestingly, ADARs can also influence miRNA abundance independent of RNA-editing. In mouse embryos where editing levels are low, ADAR2 was found to be the major ADAR protein that affects miRNA abundance. Here we extend our analysis to adult mouse brains where high editing levels are observed. Results: Using Illumina deep sequencing we compare the abundances of mature miRNAs and editing events within them, between wild-type and ADAR2 knockout mice in the adult mouse brain. Reproducible changes in abundance of specific miRNAs are observed in ADAR2 deficient mice. Most of these quantitative changes seem unrelated to A to I editing events. However, many A to G transitions in cDNAs prepared from mature miRNA sequences, reflecting A to I editing events in the RNA, are observed with frequencies reaching up to 80%. About half of these editing events are primarily caused by ADAR2 while a few miRNAs show increased editing in the absence of ADAR2, suggesting preferential editing by ADAR1. Moreover, novel, previously unknown editing events were identified in several miRNAs. In general 64% of all editing events are located within the seed region of mature miRNAs. In one of these cases retargeting of the edited miRNA could be verified in reporter assays. Also, altered processing efficiency upon editing near a processing site could be experimentally verified. Conclusions: ADAR2 can significantly influence the abundance of certain miRNAs in the brain. Only in a few cases changes in miRNA abundance can be explained by miRNA editing. Thus, ADAR2 binding to miRNA precursors, without editing them, may influence their processing and thereby abundance. ADAR1 and ADAR2 have both overlapping and distinct specificities for editing of miRNA editing sites. Over 60% of editing occurs in the seed region possibly changing target specificities for many edited miRNAs.
2014-10-02 | GSE61066 | GEO
Project description:MicroRNAs (miRNAs) are small regulatory RNAs that derive from distinctive hairpin transcripts. To learn more about the miRNAs of mammals, we sequenced 60 million small RNAs from mouse brain, ovary, testes, embryonic stem cells, three embryonic stages, and whole newborns. Analysis of these sequences confirmed 387 annotated miRNA genes and identified 110 novel miRNA genes. Over 150 previously annotated miRNAs and hundreds of candidates failed to yield sequenced RNAs with miRNA-like features. Ectopically expressing these previously proposed miRNA hairpins also did not yield small RNAs, whereas ectopically expressing the confirmed and newly identified hairpins usually did yield small RNAs with the classical miRNA features, including dependence on the Drosha endonuclease for processing. These experiments, which suggest that previous estimates of conserved mammalian miRNAs were inflated, provide a substantially revised list of confidently identified mammalian miRNAs from which to infer the general features of mammalian miRNAs. Our analyses also revealed new aspects of miRNA biogenesis and modification, including tissue-specific strand preferences, sequential Dicer cleavage of a metazoan pre-miRNA, newly identified instances of miRNA editing, and evidence for widespread Lin28-like miRNA regulation. For miRNA discovery, small RNAs were sequenced from mouse brain, ovary, testes, three embryonic stages, and whole newborns; for ectopic over-expression assays, pre-miRNA hairpins and the surrounding regions were transfected into HEK293T, and the small RNA were sequenced from the transfected cells 39-48 hours after transfection.
2010-04-26 | E-GEOD-20384 | biostudies-arrayexpress
Project description:MicroRNAs (miRNAs) play an important role in organ development. MicroRNA expression profiling is an effective method of acquiring novel and valuable information. In this study, using miRNA microarray technology, we finally validate three over-expressed miRNAs (hsa-miR-1246, hsa-miR-1323 and hsa-miR-93) and one under-expressed miRNA (hsa-miR-143*) in NSCP group. Target gene WNT5A of hsa-miR-143* was up-regulated, while target gene FGFR2 of hsa-miR-1246, hsa-miR-1323 and hsa-miR-93 was down-regulated in the NSCP group compared to the control group. The association of miRNAs expression levels with the risk of developing NSCP, the correlation with age and gender were analyzed. The risk analysis identified that odds ratio (95% CI) of hsa-miR-1246, hsa-miR-1323 and hsa-miR-93 was higher ranged from 9.75 (1.642-57.89) to 13.67 (2.480-75.30) and p＜0.05. Neither age nor gender was associated with the four miRNAs expression levels. In male cases, the association of hsa-miR-1246, hsa-miR-1323, hsa-miR-93 and hsa-miR-143* expression levels with NSCP was observed and the p value was 0.0012, 0.0008, 0.0088 and 0.0385, respectively. Bioinformatics approaches identified nine KEGG pathways enriched in predicted target genes. In summary, we firstly defined miRNAs profiles and target genes in human soft palate tissue. Four distinctive miRNAs and their target genes expression in NSCP will advance our understanding of the genetic progress of this complex disease. Further exploration will be needed to elucidate how these miRNAs and target genes modulate signaling pathways during palatogenesis.
2013-06-14 | GSE47939 | GEO
Project description:Little is known about the alterations in microRNA (miRNA) expression patterns during the consecutive stages of cervical cancer development and their association with chromosomal instability and epigenetic changes. We integrated miRNA expression profiles in normal cervical squamous epithelium, high-grade precancerous lesions (CIN2-3), squamous cell carcinomas (SCC) and adenocarcinomas (AdCAs) with previously generated chromosomal profiles of the same samples. In addition, the DNA methylation status of downregulated miRNAs located in a CpG island was determined. Significantly differential expression during the consecutive stages of cervical SCC development was observed for 106 miRNAs. Altered expression of 5 significantly differentially expressed miRNAs, hsa-miR-9 (1q23.2), hsa-miR-15b (3q25.32), hsa-miR-28-5p (3q27.3), hsa-miR-100 and hsa-miR-125b (both 11q24.1) was directly linked to frequent chromosomal alterations. Another 9 significantly downregulated miRNAs were located within a CpG island. Three of these 9 miRNAs, hsa-miR-203, hsa-miR-572, and hsa-miR-638, showed increased methylation in cervical cancer cell lines and HPV-immortalised cells compared to primary keratinocytes. Functional analyses were performed for hsa-miR-9, representing a potential oncogene with increased expression linked to a chromosomal gain, and hsa-miR-203, representing a potential tumour suppressor gene silenced by DNA methylation. Hsa-miR-9 and hsa-miR-203 were found to alter cell viability and anchorage independent growth in vitro, respectively, supporting their oncogenic and tumour suppressive function in cervical cancer. In conclusion, differential expression of 106 miRNAs, partly associated with chromosomal alterations and epigenetic changes, was observed during cervical SCC development. Altered expression of hsa-miR-9 and hsa-miR-203 was shown to be functionally relevant, underlining the importance of deregulated miRNA expression in cervical carcinogenesis.
2012-06-28 | GSE30656 | GEO