Chromatin accessibility analysis of inducible HOTAIR overexpression mouse breast cancer cells
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ABSTRACT:
PROVIDER: PRJNA832262 | ENA |
REPOSITORIES: ENA
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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: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:Transcriptome analysis of inducible HOTAIR overexpression mouse breast cancer cells
| PRJNA832261 | ENA
Project description:Study of the transcriptome changes upon Hotair overexpression in wt and Ezh2-/- Human breast cancer cell lines
2016-08-12 | GSE72524 | GEO
Project description:MDA-MB-231 Breast Cancer Cells were infected by retroviral expression with either VECTOR or HOTAIR. To test the role of polycomb in HOTAIR mediated gene expression, MDA-MB-231 HOTAIR cells were infected with short hairpin retroviral vectors targeting SUZ12 or EZH2. A genetic modification design type is where an organism(s) has had genetic material removed, rearranged, mutagenized or added, such as knock out. genetic_modification_design
2010-04-15 | E-GEOD-20435 | biostudies-arrayexpress
Project description:MDA-MB-231 Breast Cancer Cells were infected by retroviral expression with either VECTOR or HOTAIR. To test the role of polycomb in HOTAIR mediated gene expression, MDA-MB-231 HOTAIR cells were infected with short hairpin retroviral vectors targeting SUZ12 or EZH2. A genetic modification design type is where an organism(s) has had genetic material removed, rearranged, mutagenized or added, such as knock out.
2010-04-15 | GSE20435 | GEO
Project description:The long-non-coding HOX transcript antisense intergenic RNA (HOTAIR) was identified as significantly upregulated in breast ductal carcinoma in situ (DCIS). The aim of this study was to characterize the phenotypic effects and signaling pathways modulated by HOTAIR in early-stage breast cancer progression. We determined that HOTAIR induces premalignant phenotypic changes by increasing cell proliferation, migration, invasion and in vivo growth in normal and DCIS breast cell lines. Transcriptomic studies (RNA-seq) identified the main signaling pathways modulated by HOTAIR which include bioprocesses related to cell migration, epithelial to mesenchymal transition, extracellular matrix remodeling and activation of HIF1A, AP1 and FGFR signaling pathways among others. Similar pathways were identified as activated in primary invasive breast carcinomas with HOTAIR over-expression. We conclude that HOTAIR over-expression behaves as a positive regulator of cell growth and migration both in normal and DCIS breast cells involved with early-stage breast cancer progression.
2021-11-01 | GSE183058 | GEO
Project description:Expression of HOX transcript antisense intergenic RNA (HOTAIR)—a long intergenic non-coding RNA (lincRNA)—has been examined in a variety of human cancers, and overexpression of HOTAIR is correlated with poor survival among breast, colon, and liver cancer patients. In this retrospective study, we examine HOTAIR expression in 164 primary breast tumors, from patients who do not receive adjuvant treatment, in a design that is paired with respect to the traditional prognostic markers. We show that HOTAIR expression differs between patients with or without a metastatic endpoint, respectively. Survival analysis shows that high HOTAIR expression in primary tumors is significantly associated with worse prognosis independent of prognostic markers. This association is even stronger when looking only at estrogen receptor (ER)-positive tumor samples. In ER-negative tumor samples, it is not possible to detect a prognostic value of HOTAIR expression. These results are successfully validated in an independent dataset with similar associations. Furthermore, we find that high HOTAIR expression is associated with strong positive expression of multiple neighboring HOXC genes of the HOXC locus on chromosome 12q13.13 and have both negative and positive correlation with other genes located on different chromosomes. Independent datasets verify these significant correlations and thus indicate that HOTAIR might regulate additional genes than those previously reported. In conclusion, our findings suggest that HOTAIR expression may serve as an independent biomarker for the prediction of the risk of metastasis in ER-positive breast cancer patients. 164 breast cancer samples
2013-11-29 | E-GEOD-48408 | biostudies-arrayexpress
Project description:Inducible lncRNA transgenic mice reveal continual role of HOTAIR in promoting breast cancer metastasis
| PRJNA833338 | ENA
Project description:Expression of HOX transcript antisense intergenic RNA (HOTAIR)—a long intergenic non-coding RNA (lincRNA)—has been examined in a variety of human cancers, and overexpression of HOTAIR is correlated with poor survival among breast, colon, and liver cancer patients. In this retrospective study, we examine HOTAIR expression in 164 primary breast tumors, from patients who do not receive adjuvant treatment, in a design that is paired with respect to the traditional prognostic markers. We show that HOTAIR expression differs between patients with or without a metastatic endpoint, respectively. Survival analysis shows that high HOTAIR expression in primary tumors is significantly associated with worse prognosis independent of prognostic markers. This association is even stronger when looking only at estrogen receptor (ER)-positive tumor samples. In ER-negative tumor samples, it is not possible to detect a prognostic value of HOTAIR expression. These results are successfully validated in an independent dataset with similar associations. Furthermore, we find that high HOTAIR expression is associated with strong positive expression of multiple neighboring HOXC genes of the HOXC locus on chromosome 12q13.13 and have both negative and positive correlation with other genes located on different chromosomes. Independent datasets verify these significant correlations and thus indicate that HOTAIR might regulate additional genes than those previously reported. In conclusion, our findings suggest that HOTAIR expression may serve as an independent biomarker for the prediction of the risk of metastasis in ER-positive breast cancer patients.
2013-11-29 | GSE48408 | GEO