Identification and validation of NOL5A and RPS2 as potential therapeutic targtes in colorectal cancer
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE15212 | GEO | 2010/06/01
SECONDARY ACCESSION(S): PRJNA116453
REPOSITORIES: GEO
Similar Datasets
Project description:Identification and validation of NOL5A and RPS2 as potential therapeutic targets in colorectal cancer using a functional genomics approach. To identify potential therapeutic targets for colorectal cancer, we first assessed the functional and molecular consequences of RNAi mediated silencing of candidate genes derived from previously performed gene expression analyses. We then generated gene expression signatures after RNAi against HMGA1, RRM2, TACSTD2, RPS2, and NOL5A. To assess the consequences of silencing specific genes on global gene expression levels, triplicate transfections were independently performed. Cells for lyzed 48 hours or 72 hours after transfection (depending on the target gene), and total RNA was isolated for each transfection. For each sample, one array experiment was subsequently performed.
2010-06-08 | E-GEOD-15212 | biostudies-arrayexpress
Project description:Colorectal cancer (CRC) with high rate of mortality is one of the most commonly diagnosed cancers in worldwide. Advanced colorectal cancer is often accompanied by malignant proliferation of tumor cells. Further researches on colorectal cancer proliferation to find new targets and develop new therapeutic regimen are an important direction for colorectal cancer treatment. In this study, genome-wide RNAi screening was used to discover the essential genes associated with colorectal cancer cell proliferation. We found DKC1 (dyskerin pseudouridine synthase 1) promoted CRC proliferation through binding and modifying ribosomal proteins (RPL10A, RPL22L1, RPL34, RPS3) mRNA to increase the mRNAs stability and eventually increasing their expression. Besides, DKC1 is highly expressed in colorectal cancer and its aberrantly high expression is associated with poor prognosis of colorectal cancer patients. These results suggest that DKC1 could be a new therapeutic target for colorectal cancer.
2021-02-08 | PXD018103 | 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:Identification and validation of NOL5A and RPS2 as potential therapeutic targtes in colorectal cancer
| PRJNA116453 | ENA
Project description:The Trophoblast cell surface antigen 2 (TROP2) is a transmembrane glycoprotein encoded by the Tumor associated calcium signal transducer 2 (TACSTD2) gene. TROP2 is upregulated in many human malignancies including colorectal cancer, and its overexpression correlates with tumor progression, invasiveness, and poor survival. Functional studies revealed that TROP2 may have a role as both an oncogene and a tumor suppressor. To identify TROP2 function in human cancer cells, we performed gene expression profiling of TROP2+ and TROP2- cells isolated from human colon tumors.
2022-11-30 | E-MTAB-11466 | biostudies-arrayexpress
Project description:Chimeric RNAs have been used as biomarkers and therapeutic targets for multiple types of cancers. However, less attention has been paid to their mechanism of action in neoplasia. Here, we report that chimeric RNA RRM2-C2orf48 promotes 4-(methyl nitrosamine)-1-(3-pyridinyl)-1-butanone (NNK)-induced lung cancer. We found that RRM2-C2orf48 had higher expression levels in lung cancer cell lines and in lung cancer tissues from 74 patients than in normal cells and tissues, respectively. And its expression level was correlated with smoking. Next, we demonstrate that the expression level of RRM2-C2orf48 could increase after treatment with 200 mg/L NNK for 24 h. Overexpressing RRM2-C2orf48 accelerated the process of NNK-induced lung cancer and promoted cell growth. Meanwhile, suppressing RRM2-C2orf48 inhibited cell growth. Finally, we identified miR-219a-2-3p as a potential target of RRM2-C2orf48. In summary, RRM2-C2orf48 accelerated the process of NNK-induced lung cancer and miR-219a-2-3p may be involved in this process.
2022-11-19 | GSE217991 | GEO
Project description:Tumor Associated Calcium Signal Transducer 2 (TACSTD2) is one of the cancer-related genes whose overexpression correlates with tumor progression and invasiveness in human colorectal cancer. TACSTD2 gene encodes for a transmembrane glycoprotein TROP2, which is implicated in altered expression of epithelial-mesenchymal transition (EMT) markers and may play a role in metastasis formation. To determine how TROP2 affects aberrant tumor cell signaling, we isolated early adenoma cells from the mouse small intestine 6 weeks after disruption of the Adenomatous polyposis coli (Apc) gene, one of the first steps in the development of colorectal cancer in human. We performed expression profiling of Trop2+ and Trop2- tumor cells and, in addition, non-tumor cells of the intestinal epithelium, including predominantly differentiated cells.
2022-11-29 | E-MTAB-11382 | biostudies-arrayexpress