The lncRNA HOTAIR Modulates DNA-Methylation in Mesenchymal Stem Cells via Triple Helix Formation (methylation)
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE69491 | GEO | 2016/11/22
SECONDARY ACCESSION(S): PRJNA285782
REPOSITORIES: GEO
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Project description:Long non coding RNAs are implemented in epigenetic changes and regulation of gene expression. HOTAIR is a promising lncRNA concerning epigenetic regulation. We performed HOTAIR overexpression and knockdown experiments in mesenchymal stromal cells derived from bone marrow. After two weeks cells were harvested and RNA and DNA were isolated. Analysis of gene expression was performed with Human Gene 2.0 ST Array (Affymetrix, Santa Clara, USA). Analysis of DNA methylation was performed with Infinium HumanMethylation450 BeadChips (Illumina, San Diego, USA)
2016-11-22 | GSE69492 | GEO
Project description:This study demonstrated the effects of lncRNA HOTAIR knockdown on the glioma proteomics. An abnormally high expression of the lncRNA HOTAIR has been previously demonstrated in glioma cells. HOTAIR regulates genes by anchoring epigenetic modification proteins and causes abnormalities in multiple signaling pathways. We knocked down HOTAIR in glioma cells by siRNA with SILAC labeling, and then total protein was extracted for proteome mass spectrometry.
2021-12-31 | PXD029919 |
Project description:Objective: Abdominal adiposity is strongly associated with diabetic and cardiovascular comorbidities. The long non-coding RNA HOTAIR (HOX Transcript Antisense Intergenic RNA) is an important epigenetic regulator, with fat depot-specific expression between abdominal subcutaneous adipose tissue (SAT) and gluteal SAT. HOTAIR locates closely with HOXC13, known to strongly associated with human fat distribution. Here, we examined the phenotypic effects of HOTAIR overexpression on abdominal adipogenesis, and hypothesized that HOTAIR-mediated DNA methylation is correlated with transcriptome changes, leading to the regulation of specific genes and the functional pathways. Methods: The expression level of HOTAIR was compared among different fat-depots collected from six healthy, five severe obese, and five uremic subjects, and was correlated with dual-energy x-ray absorptiometry (DXA) defined regional adiposity. The human immortalized preadipocyte was used to assess the phenotypic effects of HOTAIR overexpression on abdominal adipogenesis. The integrative analysis of reduced representation bisulfite sequencing (RRBS) and RNA-sequencing was performed to identify putative genes that are epigenetically regulated by HOTAIR, and the associated signaling pathways. HOTAIR-repressed genes were further validated using RNA/chromatin immunoprecipitation with real-time qPCR and correlated with human body fat distribution. Results: We found that the expression of HOTAIR was high in gluteal SAT, and low in arm/abdominal SAT and visceral (omental) adipose tissue. It could be aberrantly increased in uremic arm SAT. Notably, in severe obese subjects we found that HOTAIR is lowly expressed in abdominal SAT correlating with a higher abdominal adiposity, whereas in uremic patients HOTAIR is highly expressed in arm SAT correlating with lower arm adiposity. HOTAIR overexpression in human immortalized abdominal preadipocyte remarkably suppresses the in vitro adipogenesis. Overall the differentially methylated genes were functionally enriched for nervous system development. We specifically identified 10 HOTAIR-mediated genes showing strong changes of DNA methylation associated with gene expression during abdominal adipogenesis, suggesting potential epigenetic regulation. Two HOTAIR-repressed genes, SLITRK4 and PITPNC1, were further highlighted and validated; presenting an obesity-driven fat-depot specific expression pattern positively correlated with the central body fat distribution. Conclusions: Our study indicated that HOTAIR is an important regulator for abdominal adipogenesis via intricate DNA methylation likely to associate with transcriptional regulation of specific genes, such as SLITRK4 and PITPNC1.
2022-04-20 | GSE186159 | GEO
Project description:Both genetic and epigenetic aberrations are linked by intricate crosstalk, and can either individually or in synergy lead to the development of cancer. Accumulating evidence suggests that epigenetic changes such as alterations in DNA methylation play a crucial role in ESCC. We performed a Illumina Infinium HumanMethylation450 BeadChip to examine the global methylation signature of esophageal squamous cell carcinoma of Chinese patients. DNA methylation profiles of esophageal squamous cell carcinoma (4 samples), paired adjacent normal surrounding tissues (4 samples) and normal esophagus mucosa from healthy individuals (4 samples) were generated using Infinium methylation 450K BeadChips from Illumina (Illumina, San Diego, USA).
2014-11-03 | E-GEOD-52826 | biostudies-arrayexpress
Project description:LincRNA HOTAIR was expressed in pure SCLC and higher expression was significantly related to lymphatic invasion and relapse. Multivariate analyses demonstrated that HOTAIR expression correlated with RFS. In vitro experiments demonstrated that half of SCLC cell lines expressed HOTAIR at higher levels than normal cells and that, using cells of SBC-3, knockdown of HOTAIR decreased proliferative activity and cellular invasiveness with altered expression of cell adhesion-related genes. Total RNAs from one siHOTAIR-transfected SBC-3 cells and control cells (siGFP-transfected cells), were extracted using RNeasy mini kit Plus (Qiagen) and hybridized to the microarrays, Sure Print G3 Human GE 8x60K microarrays (Agilent Technologies, Santa Clara, CA, USA), according to the manufacturerM-bM-^@M-^Ys instructions. Subsequently, data analysis was carried out using the GeneSpring GX 12 software (Agilent Technologies), with a stringency of P<0.1 and a 2-fold or more change using gene ontology analysis.
2014-03-05 | E-GEOD-43877 | biostudies-arrayexpress
Project description:Accumulating evidence highlights the role of long non-coding RNAs (lncRNA) in cellular homeostasis, and their dysregulation in disease settings. Most lncRNAs function by interacting with proteins or protein complexes. While several orthogonal methods have been developed to identify these proteins, each method has its inherent strengths and limitations. Here, we combine two RNA-centric methods ChIRP-MS and RNA-BioID to obtain a comprehensive list of proteins that interact with the well-known lncRNA HOTAIR. Overexpression of HOTAIR has been associated with a metastasis-promoting phenotype in various cancers. Although HOTAIR is known to bind with PRC2 and LSD1 protein complexes, an unbiased and comprehensive method to map its interactome has not yet been performed. Both ChIRP-MS and RNA-BioID data sets show an association of HOTAIR with mitoribosomes, suggesting HOTAIR has functions independent of its (post-)transcriptional mode-of-action.
2022-02-15 | PXD029057 | Pride
Project description:HOTAIR is a 2.2 kb long noncoding RNA (lncRNA) whose dysregulation has been linked to oncogenesis, defects in pattern formation during early development, and irregularities during the process of epithelial-to-mesenchymal transition (EMT). However, the oncogenic transformation determined by HOTAIR in vivo and its impact on chromatin dynamics are incompletely understood. Here we generate a transgenic mouse model with doxycycline-inducible expression of human HOTAIR in the context of the MMTV-PyMT breast cancer-prone background (iHOT-PyMT mice) to systematically interrogate the cellular mechanisms by which human HOTAIR lncRNA acts to promote breast cancer progression. We isolated breast cancer cells from the primary tumors of iHOT-PyMT mice (named iHOT+ cells) and performed RNA-seq and ATAC-seq of iHOT+ cells treated with 3 conditions: Dox+, Dox- and DoxWD. We showed that HOTAIR overexpression altered both the cellular transcriptome and chromatin accessibility landscape of multiple metastasis-associated genes and promoted epithelial to mesenchymal transition. These alterations are abrogated within several cell cycles after HOTAIR expression is reverted to basal levels, indicating an erasable lncRNA-associated epigenetic memory. These results suggest that a continual role for HOTAIR in programming a metastatic gene regulatory program.
2023-01-10 | GSE201582 | GEO
Project description:HOTAIR is a 2.2 kb long noncoding RNA (lncRNA) whose dysregulation has been linked to oncogenesis, defects in pattern formation during early development, and irregularities during the process of epithelial-to-mesenchymal transition (EMT). However, the oncogenic transformation determined by HOTAIR in vivo and its impact on chromatin dynamics are incompletely understood. Here we generate a transgenic mouse model with doxycycline-inducible expression of human HOTAIR in the context of the MMTV-PyMT breast cancer-prone background (iHOT-PyMT mice) to systematically interrogate the cellular mechanisms by which human HOTAIR lncRNA acts to promote breast cancer progression. We isolated breast cancer cells from the primary tumors of iHOT-PyMT mice (named iHOT+ cells) and performed RNA-seq and ATAC-seq of iHOT+ cells treated with 3 conditions: Dox+, Dox- and DoxWD. We showed that HOTAIR overexpression altered both the cellular transcriptome and chromatin accessibility landscape of multiple metastasis-associated genes and promoted epithelial to mesenchymal transition. These alterations are abrogated within several cell cycles after HOTAIR expression is reverted to basal levels, indicating an erasable lncRNA-associated epigenetic memory. These results suggest that a continual role for HOTAIR in programming a metastatic gene regulatory program.
2023-01-10 | GSE201581 | GEO
Project description:Changes in gene expression profile of CLL cells in response to an antigen-specific Th cell clone that is specific for a Ckappa peptide of mouse Abs. Mouse anti human BCR mAbs were used to ligate BCR and deliver antigen to CLL cells. 32-45 x10e6 PBMC were incubated overnight with or without 2 μg/ml of Ms κ+IgG anti-kappa and anti-lambda mAbs. The PBMC were then cultured in presence or absence of 12.5 x10e6 T18 cells. On day 3, CLL cells were purified by negative selection using CD3 and CD14 Dynabeads (Invitrogen). RNA from CLL cells was controlled and quantified on a NanoDrop1000 (Thermo Scientific, Wilmington, DE, USA). 290ng per sample was amplified and labeled with the TotalPrep™-96 RNA Amplification Kit (Illumina, San Diego, CA, USA). Sample quality was further tested by Agilent 2100 bioanalyzer (Agilent, Santa Clara, CA, USA). 1500ng of biotin labeled cRNA was used to hybridize onto Illumina HumanWG-6 v3 Expression BeadChips. After scanning, the results were imported into Illumina GenomeStudio v. 2010.1, Gene Expression module v. 1.6.0 for quality control and data export. Analysis was performed utilizing GeneSpring GX v11 software (Agilent, Santa Clara, CA, USA). In GeneSpring GX, Logbase 2-transformed data were normalized to the 75 percentile with baseline transformation to median of all samples. Flag Information: Lower cutoff for 'Present' call: 0.8, Upper cutoff for 'Absent' call: 0.6
2013-08-08 | GSE48268 | GEO
Project description:Accumulating evidence highlights the role of long non-coding RNAs (lncRNA) in cellular homeostasis, and their dysregulation in disease settings. Most lncRNAs function by interacting with proteins or protein complexes. While several orthogonal methods have been developed to identify these proteins, each method has its inherent strengths and limitations. Here, we combine two RNA-centric methods ChIRP-MS and RNA-BioID to obtain a comprehensive list of proteins that interact with the well-known lncRNA HOTAIR. Overexpression of HOTAIR has been associated with a metastasis-promoting phenotype in various cancers. Although HOTAIR is known to bind with PRC2 and LSD1 protein complexes, an unbiased and comprehensive method to map its interactome has not yet been performed. Both ChIRP-MS and RNA-BioID data sets show an association of HOTAIR with mitoribosomes, suggesting HOTAIR has functions independent of its (post-)transcriptional mode-of-action.
2022-02-15 | PXD029058 | Pride