Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA314258 | ENA |
REPOSITORIES: ENA
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Project description:Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer associated with poor survival outcomes. Aldehyde dehydrogenase 1A3 (ALDH1A3) promotes tumor growth, metastasis, and chemoresistance across multiple cancer types including TNBC, glioblastoma, melanoma lung, and colon cancers. Currently, there are no ALDH1A3 inhibitors in clinic and developing targeted ALDH1A3 inhibitors is novel precision medicine approach to treat ALDH1A3+ tumors. For this purpose, we have developed a novel ALDH1A3 specific inhibitor,CLM296
2026-01-28 | GSE293106 | GEO
Project description:Tumor necrosis factor-α-inducible protein 8 (TNFAIP8) is a TNF-α inducible anti-apoptotic protein involved in tumor growth and survival. The effect and biological significance of TNFAIP8 over-expression on the global gene expression in prostate cancer PC3 cells was analysed. Retinoic Acid Receptor Responder (RARRES1)/ Tazarotene-induced gene-1 (TIG-1) is a putative tumor suppressor gene. The effect of RARRES1 over-expression on the global gene expression was also analysed in order to determine the significance of RARRES1 in prostate cancer PC3 cells.
2018-12-30 | E-MTAB-6803 | biostudies-arrayexpress
Project description:Tumor suppressor genes (TSGs) are sometimes inactivated by transcriptional silencing through promoter hypermethylation. To identify novel methylated TSGs in melanoma, we carried out global mRNA expression profiling on a panel of 12 melanoma cell lines treated with a combination of 5-Aza-2-deoxycytidine (5AzadC) and an inhibitor of histone deacetylase, Trichostatin A. Reactivation of gene expression after drug treatment was assessed using Illumina whole-genome microarrays. After qRT-PCR confirmation, we followed up 8 genes (AKAP12, ARHGEF16, ARHGAP27, ENC1, PPP1R3C, PPP1R14C, RARRES1, and TP53INP1) by quantitative DNA methylation analysis using mass spectrometry of base-specific cleaved amplification products in panels of melanoma cell lines and fresh tumors. PPP1R3C, ENC1, RARRES1, and TP53INP1, showed reduced mRNA expression in 35–59% of the melanoma cell lines compared to melanocytes and which was correlated with a high proportion of promoter methylation (>40–60%). The same genes also showed extensive promoter methylation in 6–25% of the tumor samples, thus confirming them as novel candidate TSGs in melanoma.
2011-10-03 | GSE32492 | GEO
Project description:We try to explore the effect of RARRES1 on human podocyte, so we performed RARRES1 overexpression and knockdown experiments. cell mRNA profiles of human human podocyte cell lines transfected with RARRES1 overexpression vectors orcontrol vectors; and cells transfected with RARRES1 shRNA lentivirus or scramble shRNA lentivirus and stimulated with TNFa (10ng/ml) or without TNFa for 24 hours were generated by deep sequencing, in triplicate, using Illumina GAIIx. The sequence reads that passed quality filters were analyzed at the transcript. We found that most differentially expressed genes (DEGs) are enriched with cell migration and apoptosis-related pathways, also DEGs stimulated by TNFα but suppressed by RARRES1 knockdown, were also enriched with cell cycle-related pathways.These data suggest that RARRES1 plays a key role in the regulation of cell cycle and apoptosis, consistent with its role as a tumor suppressor gene.
2020-10-07 | GSE151484 | GEO
Project description:Purpose: RARRES1 is proposed as tumor suppressor gene but its function is not clear yet. To elucidate RARRES1 function in carcinogenesis, we examine phenotype and genetic characteristics of the RARRES1 genetically knockout mice lung. Methods: Genetic profiles of RARRES1 wild type and knockout mouse lung tissues of embryonic day 19.5, 10-month-old, and 18-month-old mice were analyzed by whole genome and RNA sequencing in triplicate, using Illumina Hiseq X ten. Additionally, three lung tumors originated from RARRES1 knockout mice also examine using same platform. Results: RARRES1 knockout accelerate spontaneous lung carcinogenesis, with pluripotency of stem cells, Hippo signaling pathway, Wnt signaling pathway, and cell cycle related genes are significantly activated including Nanog, CDK1, Cyclin E. In addition, RARRES1 knockout induced lung cancer had rare oncogenic mutations, on the contrary, lung tissue progenitor cell, lung bipotent progenitor cell and AT2 type cell popularity increased. Conclusions: RARRES1 knockout accelerate spontaneous lung carcinogenesis through organ stem cell population enhancement with various stemness related gene set activation beside rare mutational driving.
2024-02-02 | GSE131161 | GEO
Project description:Purpose:The Vimentin gene plays a pivotal role in epithelial-to-mesenchymal transition (EMT) and is known to be over-expressed in the prognostically poor basal-like breast cancer subtype. Recent studies have reported Vimentin DNA methylation in association with poor clinical outcomes in other solid tumors, but not in breast cancer. We therefore quantified Vimentin DNA methylation in breast tumors and matched normal pairs in association with gene expression and survival in a cohort of 83 breast cancer patients. Materials and Methods:Vimentin methylation was quantified in 14 breast cell lines, 83 breast tumors, and 57 matched normal pairs using MALDI-TOF mass spectrometry. Gene expression data via qRT-PCR in cell lines, and oligo microarray data from breast tissues was correlated with percent methylation in the Vimentin promoter. A threshold of 20 percent average methylation was set for bivariate and multivariate tests of association between methylation and tumor subtype, tumor histopathology, and survival. Results:Vimentin was differentially methylated in luminal breast cancer cell lines, and in luminal A, luminal B and HER2+ breast tumor subtypes, but was rare in basal-like cell lines and tumors. Increased methylation was strongly correlated with decreased mRNA expression in cell lines, and had a moderate inverse correlation in breast tumors. Importantly, Vimentin methylation predicted poor overall survival independent of race, subtype, stage, nodal status or estrogen receptor positivity. Conclusion:Vimentin methylation predicts overall survival in breast cancer patients and holds promise as a prognostic biomarker for guiding treatment and prophylaxis. reference x sample
2013-02-19 | E-GEOD-35629 | biostudies-arrayexpress
Project description:Aldehyde dehydrogenase (ALDH1) activity has long been established as a pro-tumorigenic feature of many cancers, yet the identification of specific isoforms that are enriched in cancer, the mechanism of action of this isoform(s), and viable therapeutic strategies to target this pathway have long remained absent. Whereas one of the well-established functions of the ALDH1a family is the conversion of retinaldehyde into retinoic acid to activate nuclear retinoid signaling, the retinoid pathway is paradoxically hypothesized as a cell-intrinsic tumor suppressor pathway. Here we resolve this long-standing conflict by showing that while ALDH1a3 is broadly overexpressed across diverse cancer types, ALDH1a3 expressing tumor cells often lose the sensitivity to retinoid signaling. Instead, all-trans retinoic acid produced by ALDH1a3 acts in a paracrine fashion to suppress anti-tumor immunity and promote tumor growth. We further used structure-based high throughput screening to develop a series of first-in-class, therapeutically viable antagonists of ALDH1a3 with potent anti-tumor immunotherapeutic activity, an excellent pharmacological profile and no evidence of toxicity. Findings of this study resolve prior contradictions in the retinoid pathway through the development of highly specific and potent ALDH1a3 inhibitors.
2025-08-26 | PXD052693 | Pride
Project description:Elevated aldehyde dehydrogenase (ALDH) activity correlates with poor outcome for many solid tumors as ALDHs potentially regulate cell proliferation and chemoresistance of cancer stem cells (CSCs). ALDH1A3 is the dominant isomer of the ALDH gene family in Mesenchymal subtype of GSC cells and is highly upregulated compared to other subtype of GSCs. ALDH1A3 is an important enzyme in the synthesis of Retinoic Acid, which regulates various downstream pathways and the transcription of numerous genes. Microarray analysis of the GSCs before or after depletion of ALDH1A3 provides important information to determine the genes regulated by ALDH1A3 in the mesenchymal subtype of GSCs. We used microarrays to analyze the transcriptome change after the depletion of ALDH1A3 in GSC-326 cells that express very high levels of ALDH1A3.
2021-10-07 | GSE185463 | GEO
Project description:The development of efficacious therapies targeting metastatic spread of breast cancer to the brain represents an unmet clinical need. Accordingly, an improved understanding of the molecular underpinnings of central nervous system spread and progression of breast cancer brain metastases (BCBM) is required. In this study, the clinical burden of disease in BCBM was investigated, as well as the role of aldehyde dehydrogenase 1A3 (ALDH1A3) in the metastatic cascade leading to BCBM development. Initial analysis of clinical survival trends for breast cancer and BCBM determined improvement of breast cancer survival rates, however this has failed to positively impact the prognostic milestones of triple-negative breast cancer (TNBC) brain metastases (BM). ALDH1A3 and a representative epithelial-mesenchymal transition (EMT) gene signature (mesenchymal markers CD44, Vimentin) were compared in tumors derived from BM, lung metastases (LM) or bone metastases (BoM) of patients as well as mice post-injection of TNBC cells. Selective elevation of the EMT signature and ALDH1A3 were observed in BM, unlike LM and BoM, especially in the tumor edge. Furthermore, ALDH1A3 was determined to play a role in BCBM establishment via regulation of circulating tumor cell (CTC) adhesion and migration phases in the BCBM cascade. Validation through genetic and pharmacologic inhibition of ALDH1A3 via lentiviral shRNA knockdown and a novel small molecule inhibitor demonstrated selective inhibition of BCBM formation with prolonged survival of tumor-bearing mice. Given the survival benefits via targeting ALDH1A3, it may prove an effective therapeutic strategy for BCBM prevention and/or treatment.
2020-01-01 | GSE138361 | GEO