HMGA1: A master regulator of tumor progression in triple-negative breast cancer cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE45483 | GEO | 2015/02/18
SECONDARY ACCESSION(S): PRJNA194135
REPOSITORIES: GEO
Similar Datasets
Project description:Emerging evidence suggests that tumor cells metastasize by co-opting stem cell transcriptional networks, although the molecular underpinnings of this process are poorly understood. Here, we show for the first time that the high mobility group A1 (HMGA1) gene drives metastatic progression in triple negative breast cancer cells (MDA-MB-231) by reprogramming cancer cells to a stem-like state. We discovered an HMGA1 signature in triple negative breast cancer cells that is highly enriched in embryonic stem cells. Together, these findings indicate that HMGA1 is a master regulator of tumor progression in breast cancer by reprogramming cancer cells through stem cell transcriptional networks. Future studies are needed to determine how to target HMGA1 in therapy. HMGA1 was knocked-down in MDA-MB-231 cells using siRNA as we previously described (Tesfaye A 2007). RNA from three independent knockdown experiements along with 3 control populations were collected by Rneasy miniprep (Qiagen) and analyzed by Affymetrix Human Exon 1.0 ST platform.
2015-02-18 | E-GEOD-45483 | biostudies-arrayexpress
Project description:Analysis of MDA-MB-231 breast cancer cells depleted for High Mobility Group A1 (HMGA1) using siRNA. HMGA1 is involved in invasion and metastasis in breast cancer cells. Results identify the specific transcriptional program induced by HMGA1 in highly metastatic breast cancer cells.
2013-12-10 | GSE35525 | GEO
Project description:Analysis of MDA-MB-231 breast cancer cells depleted for High Mobility Group A1 (HMGA1) using siRNA. HMGA1 is involved in invasion and metastasis in breast cancer cells. Results identify the specific transcriptional program induced by HMGA1 in highly metastatic breast cancer cells. MDA-MB-231 cells were transfected with HMGA1-specific siRNA or a control siRNA. Transfections were performed by using Lipofectamin RNAiMAX (Invitrogen) according to the manufacturer's procedure. Seventy-two hours after transfection, samples were processed for total RNA extraction and hybridization on Affymetrix microarrays. Four biological replicas (A, B, C, D) were used for each of the two conditions, for a total of 8 samples.
2013-12-10 | E-GEOD-35525 | biostudies-arrayexpress
Project description:One of the factors involved in TNBC aggressiveness is HMGA1, a member of non-histone chromatin proteins. The High mobility group A1 is an architectural transcription factor which, by altering chromatin structure and interacting with transcription factors, can regulate the transcription of several genes. HMGA1 protein is defined as an oncofetal protein as it is highly expressed during the embryogenesis while its expression decreases or is absent in adults, and it is re-expressed in a variety of tumors, including breast cancer. Several works established that, in breast cancer, HMGA1 expression is correlated with high tumor grade and tumor metastasis, resistance to therapies and poor prognosis. The goal of this project is to find out in details, which are the genes that are modulated by HMGA1 in MDA-MB-231 triple negative breast cancer cell line model.
2019-07-29 | GSE129915 | GEO
Project description:HMGA1 is a well-established oncogene and is a master regulator in breast cancer cells controlling the shift from a non-tumorigenic epithelial-like phenotype towards a highly aggressive mesenchymal-like one. In this work we compared HMGA1-silenced versus control MDA-MB-231 by means of a label free shotgun proteomics approach and crossed these data with DNA microarray expression profile obtained on the same cells. Resulting data were then filtered for genes linked to poor prognosis in breast cancer gene expression meta-datasets. This workflow allows us to establish a small molecular signature composed by 21 members with a prognostic value as regards overall-, recurrence free-, and distant metastasis free-survival in breast cancer.
2018-10-17 | PXD002032 | Pride
Project description:Myeloproliferative neoplasms (MPN) transform to myelofibrosis (MF) and highly lethal acute myeloid leukemia (AML), although actionable mechanisms driving progression remain elusive. The HMGA1 chromatin regulator is up-regulated during MPN progression with highest levels after transformation. HMGA1 depletion in JAK2V617F MPN AML cell lines disrupts proliferation, clonogenicity, and leukemic engraftment. Surprisingly, loss of just a single Hmga1 allele prevents progression to MF in JAK2V617F transgenic mice, decreasing blood counts and expansion in stem and myeloid progenitors while preventing splenomegaly and fibrosis within the spleen and bone marrow. RNA sequencing revealed HMGA1-dependent transcriptional networks that govern proliferation (E2F, G2M, mitosis, MYC targets) and cell fate, including the GATA2 master regulatory gene. Silencing GATA2 recapitulates phenotypes observed with HMGA1 depletion whereas GATA2 re-expression partially rescues leukemogenesis. HMGA1 transactivates GATA2 through sequences near the developmental enhancer (+9.5), increasing chromatin accessibility and recruiting active histone marks. Further, HMGA1 transcriptional networks, including GATA2, are activated in human MF after leukemic transformation. Further, HMGA1 depletion synergizes with the JAK2 inhibitor, ruxolitinib, to prolong survival in murine MPN AML. These findings illuminate HMGA1 as a key epigenetic switch required for MPN transformation and promising therapeutic target to treat or prevent disease progression.
2023-10-05 | GSE197942 | GEO
Project description:Myeloproliferative neoplasms (MPN) transform to myelofibrosis (MF) and highly lethal acute myeloid leukemia (AML), although actionable mechanisms driving progression remain elusive. The HMGA1 chromatin regulator is up-regulated during MPN progression with highest levels after transformation. HMGA1 depletion in JAK2V617F MPN AML cell lines disrupts proliferation, clonogenicity, and leukemic engraftment. Surprisingly, loss of just a single Hmga1 allele prevents progression to MF in JAK2V617F transgenic mice, decreasing blood counts and expansion in stem and myeloid progenitors while preventing splenomegaly and fibrosis within the spleen and bone marrow. RNA sequencing revealed HMGA1-dependent transcriptional networks that govern proliferation (E2F, G2M, mitosis, MYC targets) and cell fate, including the GATA2 master regulatory gene. Silencing GATA2 recapitulates phenotypes observed with HMGA1 depletion whereas GATA2 re-expression partially rescues leukemogenesis. HMGA1 transactivates GATA2 through sequences near the developmental enhancer (+9.5), increasing chromatin accessibility and recruiting active histone marks. Further, HMGA1 transcriptional networks, including GATA2, are activated in human MF after leukemic transformation. Further, HMGA1 depletion synergizes with the JAK2 inhibitor, ruxolitinib, to prolong survival in murine MPN AML. These findings illuminate HMGA1 as a key epigenetic switch required for MPN transformation and promising therapeutic target to treat or prevent disease progression.
2023-10-05 | GSE189569 | GEO
Project description:Myeloproliferative neoplasms (MPN) transform to myelofibrosis (MF) and highly lethal acute myeloid leukemia (AML), although actionable mechanisms driving progression remain elusive. The HMGA1 chromatin regulator is up-regulated during MPN progression with highest levels after transformation. HMGA1 depletion in JAK2V617F MPN AML cell lines disrupts proliferation, clonogenicity, and leukemic engraftment. Surprisingly, loss of just a single Hmga1 allele prevents progression to MF in JAK2V617F transgenic mice, decreasing blood counts and expansion in stem and myeloid progenitors while preventing splenomegaly and fibrosis within the spleen and bone marrow. RNA sequencing revealed HMGA1-dependent transcriptional networks that govern proliferation (E2F, G2M, mitosis, MYC targets) and cell fate, including the GATA2 master regulatory gene. Silencing GATA2 recapitulates phenotypes observed with HMGA1 depletion whereas GATA2 re-expression partially rescues leukemogenesis. HMGA1 transactivates GATA2 through sequences near the developmental enhancer (+9.5), increasing chromatin accessibility and recruiting active histone marks. Further, HMGA1 transcriptional networks, including GATA2, are activated in human MF after leukemic transformation. Further, HMGA1 depletion synergizes with the JAK2 inhibitor, ruxolitinib, to prolong survival in murine MPN AML. These findings illuminate HMGA1 as a key epigenetic switch required for MPN transformation and promising therapeutic target to treat or prevent disease progression.
2023-10-05 | GSE189568 | GEO
Project description:Myeloproliferative neoplasms (MPN) transform to myelofibrosis (MF) and highly lethal acute myeloid leukemia (AML), although actionable mechanisms driving progression remain elusive. The HMGA1 chromatin regulator is up-regulated during MPN progression with highest levels after transformation. HMGA1 depletion in JAK2V617F MPN AML cell lines disrupts proliferation, clonogenicity, and leukemic engraftment. Surprisingly, loss of just a single Hmga1 allele prevents progression to MF in JAK2V617F transgenic mice, decreasing blood counts and expansion in stem and myeloid progenitors while preventing splenomegaly and fibrosis within the spleen and bone marrow. RNA sequencing revealed HMGA1-dependent transcriptional networks that govern proliferation (E2F, G2M, mitosis, MYC targets) and cell fate, including the GATA2 master regulatory gene. Silencing GATA2 recapitulates phenotypes observed with HMGA1 depletion whereas GATA2 re-expression partially rescues leukemogenesis. HMGA1 transactivates GATA2 through sequences near the developmental enhancer (+9.5), increasing chromatin accessibility and recruiting active histone marks. Further, HMGA1 transcriptional networks, including GATA2, are activated in human MF after leukemic transformation. Further, HMGA1 depletion synergizes with the JAK2 inhibitor, ruxolitinib, to prolong survival in murine MPN AML. These findings illuminate HMGA1 as a key epigenetic switch required for MPN transformation and promising therapeutic target to treat or prevent disease progression.
2023-10-05 | GSE183374 | GEO
Project description:Cholangiocarcinoma (CHOL) is a malignancy arising from either the intrahepatic or the extrahepatic bile ducts which carries a severe prognosis. HMGA1 is a transcription factor which has a high expression level in many types of cancer. In this study, we find HMGA1 overexpression in CHOL. In order to investigate the regulatory mechanism of HMGA1 in CHOL, we performed RNA-seq in HUCCT1 cells with HMGA1 knock down compared with control in three repeat.
2021-11-03 | GSE163759 | GEO