Project description:<p>BRCA1 mutations are a hallmark of hereditary ovarian cancer, strongly linked to deficiencies in homologous recombination (HR) DNA repair and impaired DNA replication fork protection. However, its roles in cancer progression beyond maintaining genomic integrity remain poorly understood. Through metabolomics approaches, we found BRCA1-deficiency strikingly increased choline metabolism. Loss of BRCA1 promotes choline uptake through upregulating choline transporter-like protein 4 (CTL4). BRCA1 directly binds and recruits EZH2-mediated H3K27Me3 deposition to CTL4 promoter. CTL4 was therefore overexpressed in ovarian cancer tissues with BRCA1 mutations. Furthermore, BRCA1-deficiency significantly promotes ovarian cancer invasion, while inhibition of CTL4 reverses the high metastatic potential of BRCA1-deficient ovarian cancer cells, suggesting the functionality and specificity of CTL4 as a therapeutic target. Additionally, we discovered that phosphocholine, the choline metabolite increased by CTL4 overexpression, interacted with and stabilized the epithelial-to-mesenchymal transition inducer FAM3C in BRCA1-deficient ovarian cancer cells. Importantly, we identified a potent CTL4 inhibitor, DT-13, which significantly reduces choline metabolism and effectively suppresses metastasis in BRCA1-deficient ovarian cancers. Therefore, our study uncovers a mechanism underlying metastasis in BRCA1-deficient cancers and identifies CTL4 as a therapeutic target for metastatic ovarian cancer patients with BRCA1 mutations.</p>
Project description:Gene expression analysis was also performed on 13 primary and established human ovarian cancer cell lines (A2008, OAW42, OVCAR2, OVCAR3, OVCAR4, OVCAR5, OVCAR8, OVCAR10, OV7M, OV95, PE01, PE04, SKOV3) using Affymetrix Human Gene 1.0 ST Arrays The study focused on ovarian cancer chemokine expressions
Project description:Gene expression analysis was also performed on 13 primary and established human ovarian cancer cell lines (A2008, OAW42, OVCAR2, OVCAR3, OVCAR4, OVCAR5, OVCAR8, OVCAR10, OV7M, OV95, PE01, PE04, SKOV3) using Affymetrix Human Gene 1.0 ST Arrays
Project description:Gene expression profiling of immortalized human mesenchymal stem cells with hTERT/E6/E7 transfected MSCs. hTERT may change gene expression in MSCs. Goal was to determine the gene expressions of immortalized MSCs.
Project description:Transcriptional profiling of human mesenchymal stem cells comparing normoxic MSCs cells with hypoxic MSCs cells. Hypoxia may inhibit senescence of MSCs during expansion. Goal was to determine the effects of hypoxia on global MSCs gene expression.
Project description:Gene methylation profiling of immortalized human mesenchymal stem cells comparing HPV E6/E7-transfected MSCs cells with human telomerase reverse transcriptase (hTERT)- and HPV E6/E7-transfected MSCs. hTERT may increase gene methylation in MSCs. Goal was to determine the effects of different transfected genes on global gene methylation in MSCs.
Project description:Gene expression profiling of immortalized human mesenchymal stem cells with hTERT/E6/E7 transfected MSCs. hTERT may change gene expression in MSCs. Goal was to determine the gene expressions of immortalized MSCs. One-condition experment, gene expression of 3A6