Effect of the expression of ELOVL5 and IGFBP6 genes on the metastatic potential of breast cancer cells
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PROVIDER: PRJNA698352 | ENA |
REPOSITORIES: ENA
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Project description:Previously, it was shown that expression of ELOVL5 and IGFBP6 genes is associated with the risk of the formation of distant metastases in breast cancer. In this work, we studied the change in phenotypical traits, as well as in the transcriptomic and proteomic profiles of breast cancer cells as a result of knockdown of ELOVL5 and IGFBP6 genes.
2021-02-01 | GSE165854 | GEO
Project description:Identification of changes in protein expression by label-free shotgun proteomics in breast cancer MDA-MB-231 cells with knockdown of ELOVL5 and IGFBP6 genes in comparison with control MDA-MB-231 cells.
2021-05-20 | PXD023892 | Pride
Project description:Breast cancer (BC) is the leading cause of death from malignant neoplasms among women worldwide, and metastatic BC presents the biggest problems for treatment. Previously, it was shown that lower expression of ELOVL5 and IGFBP6 genes is associated with a higher risk of the formation of distant metastases in BC. In this work, we studied the change in phenotypical traits, as well as in the transcriptomic and proteomic profiles of BC cells as a result of the stable knockdown of ELOVL5 and IGFBP6 genes. The knockdown of ELOVL5 and IGFBP6 genes was found to lead to a strong increase in the expression of the matrix metalloproteinase (MMP) MMP1. These results were in good agreement with the correlation analysis of gene expression in tumor samples from patients and were additionally confirmed by zymography. The knockdown of ELOVL5 and IGFBP6 genes was also discovered to change the expression of a group of genes involved in the formation of intercellular contacts. In particular, the expression of the CDH11 gene was markedly reduced, which also complies with the correlation analysis. The spheroid formation assay showed that intercellular adhesion decreased as a result of the knockdown of the ELOVL5 and IGFBP6 genes. Thus, the obtained data indicate that malignant breast tumors with reduced expression of the ELOVL5 and IGFBP6 genes can metastasize with a higher probability due to a more efficient invasion of tumor cells.
| S-EPMC8206645 | biostudies-literature
Project description:It has previously been reported that expression levels of insulin-like growth factor binding protein 6 (IGFBP6) are reduced in unstable plaques compared to stable plaques in patients with coronary heart disease (CAD). However, the exact role and mechanism of IGFBP6 in endothelial homeostasis and inhibition of focal atherosclerotic plaque development in vivo remains unclear. Transcripome sequencing and bioinformatics analysis of IGFBP6-overexpressed human umbilical vein endothelial cells (HUVECs) suggest that pathway analysis and differentially expressed mRNA may help clarify the role and potential mechanism of IGFBP6 in the treatment of cardiovascular diseases.
2024-05-01 | GSE265787 | GEO
Project description:Fatty acid is a main component of lipid. The differences of chain-length and pattern of saturation / desaturation in fatty acid are essential for diversity of biological lipid functions. Elongation of very-long-chain fatty acids (ELOVL) plays a critical role in regulating the elongation of fatty acid and ELOVL 1 to 7 are reported in the present. In several cancers but renal cell carcinoma (RCC), the relationship between ELOVLs and cancer progression has been reported. In TCGA cohort, ELOVL5 expression is associated with advanced TNM stage and poor prognosis. We performed CRISPR-Cas9 targeted knockout of ELOVL5 in 2 different RCC cell lines, ACHN and 786-O, respectively. ELOVL5 knockout significantly suppressed cellular invasion, migration and proliferation in vitro and in vivo. In ingenuity Pathway Analysis, Akt signaling activation was decreased in ELOVL5-KO cells. In western blotting analysis, the phosphorylation level of Akt was inhibited in ELOVL5-KO cells. Resultantly, it was suggested that ELOVL5 is involved in the phosphorylation level of Akt and affects cancer progression in RCC.
2022-08-17 | GSE192403 | GEO
Project description:Acute lymphoblastic leukemia (ALL) represents the most prevalent pediatric malignancy, with acute T-lymphoblastic leukemia (T-ALL) comprising 10-25% of ALL cases. Functional studies revealed that ELOVL5 knockdown inhibited T-ALL cell proliferation and enhanced apoptosis in vitro, while in vivo experiments demonstrated that ELOVL5 suppression resulted in reduced tumor burden and extended survival. RNA-seq analysis was conducted and the differently expressed genes were revealed in the ELOVL5-knockdown J.gamma1 cells in comparison to control group.
2025-12-08 | GSE292865 | GEO
Project description:IGFBP6 is a secreted protein with a controversial role in human malignancies, being downregulated in the majority of human cancers, but upregulated in selected tumors. Ovarian carcinoma (OC) is a human malignancy characterized by IGFBP6 downregulation, even though the significance of its low expression during ovarian carcinogenesis is still poorly understood. IGFBP6 expression levels and the activation of its signaling pathway were evaluated in two matched OC cell lines derived from a high-grade serous ovarian cancer before and after platinum resistance (PEA1 and PEA2 cells,respectively). A whole genome gene expression analysis was comparatively performed in both cell lines upon IGFBP6 stimulation by Illumina technology. IGFBP6 gene expression in human OCs data were obtained from public datasets. Gene expression data from public datasets confirmed the downregulation of IGFBP6 from normal ovarian tissues to primary and metastatic OCs. The comparative analysis of platinum-sensitive (PEA1) and platinum-resistant (PEA2) cell lines showed quantitative and qualitative differences in the activation of IGFBP6 signaling. Indeed, IGFBP6 enhanced ERK1/2 phosphorylation only in PEA1 cells and induced a more evident and significant gene expression reprogramming in PEA1 compared to PEA2 cells. Furthermore, the analysis of selected genes modulated by IGFBP6 (i.e., FOS, JUN, TNF, IL6, IL8, and EGR1) showed an inverse regulation in PEA1 versus PEA2 cells, as well as selected hallmarks and IL-6 signaling were ositively regulated in PEA1, while inhibited in PEA2 cells.These data suggest that loss of IGFBP6 signaling may play a role in ovarian cancer progression, being likely associated to the development of platinum resistance.
2022-03-23 | GSE189717 | GEO
Project description:Introduction: Relapse of breast cancer is one of the key obstacles to successful treatment. Previously we have shown that low expression of ELOVL5 and IGFBP6 genes in breast cancer tissue corresponded to poor prognosis. ELOVL5 participates directly in the elongation of polyunsaturated fatty acids (PUFAs) that are considered to play an important role in cancer cell metabolism. Thus, in this work we studied the changes in lipid metabolism in breast cancer cells with reduced expression of either ELOVL5 or IGFBP6 gene. Methods: MDA-MB-231 cells with a stable knockdown of either ELOVL5 or IGFBP6 gene were used in this study. Transcriptomic and proteomic analysis as well as RT-PCR were utilized to assess gene expression. Content of individual fatty acids in the cells was measured with HPLC-MS. HPLC was used for analysis of the kinetics of PUFAs uptake. Cell viability was measured with MTS assay. Flow cytometry was used to measure activation of apoptosis. Fluorescent microscopy was utilized to assess accumulation of ROS and formation of lipid droplets. Glutathione peroxidase activity was measured with a colorimetric assay. Results: We found that the knockdown of IGFBP6 gene led to significant changes in the profile of fatty acids in the cells and in the expression of many genes associated with lipid metabolism. As some PUFAs are known to inhibit proliferation and cause death of cancer cells, we also tested the response of the cells to single PUFAs and to combinations of docosahexaenoic acid (DHA, a n-3 PUFA) with standard chemotherapeutic drugs. Our data suggest that external PUFAs cause cell death by activation of ferroptosis, an iron-dependent mechanism of cell death with excessive lipid peroxidation. Moreover, both knockdowns increased cells' sensitivity to ferroptosis, probably due to a significant decrease in the activity of the antioxidant enzyme GPX4. Addition of DHA to commonly used chemotherapeutic drugs enhanced their effect significantly, especially for the cells with low expression of IGFBP6 gene. Discussion: The results of this study suggest that addition of PUFAs to the treatment regimen for the patients with low expression of IGFBP6 and ELOVL5 genes can be potentially beneficial and is worth testing in a clinically relevant setting.
| S-EPMC9880435 | biostudies-literature
Project description:Long-chain fatty acid elongases ELOVL2 and ELOVL5 are key regulators of polyunsaturated fatty acid metabolism. To investigate transcriptomic changes induced by depletion of these enzymes, RNA sequencing was performed in A498 renal cancer cells following siRNA-mediated knockdown of ELOVL2 and/or ELOVL5. Transcriptomic profiles were compared among control cells, ELOVL2 knockdown cells, ELOVL5 knockdown cells, and double knockdown cells.
2026-03-16 | GSE324459 | GEO
Project description:An Engineered Niche Delineates Metastatic Potential of Breast Cancer
| PRJNA974700 | ENA