Project description:To predict differentially expressed miRNAs between monosomy 3 and disomy 3, and to associate these miRNAs with the clinico-pathological parameters in South Asian Indian population with uveal melanoma (UM). The study consists of six uveal melanoma primary tumour tissues of South Asian-Indian population. These six tumours have been screened for chromosome 3 aberration using Chromogenic in-situ hybridisation (CISH). Thus, sample under the study includes, three each of monosomy 3 and disomy 3. The miRNA profiling was carried out from the tumor sections of formalin-fixed paraffin embedded eyeball samples. miRNA expression profile was obtained in monosomy 3 and disomy 3 samples, analysed by unsupervised analysis (Principal Component Analysis) and supervised analysis (Significance analysis of microarray). The select up-regulated and candidate miRNAs associated with monosomy 3 uveal melanoma tumors were validated further with qRT-PCR (n=86). Thus, this study indicates the role of miRNAs in UM tumor progression and their implication in predetermining the liver metastasis.
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:<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:To predict differentially expressed miRNAs between monosomy 3 and disomy 3, and to associate these miRNAs with the clinico-pathological parameters in South Asian Indian population with uveal melanoma (UM). The study consists of six uveal melanoma primary tumour tissues of South Asian-Indian population. These six tumours have been screened for chromosome 3 aberration using Chromogenic in-situ hybridisation (CISH). Thus, sample under the study includes, three each of monosomy 3 and disomy 3. The miRNA profiling was carried out from the tumor sections of formalin-fixed paraffin embedded eyeball samples. miRNA expression profile was obtained in monosomy 3 and disomy 3 samples, analysed by unsupervised analysis (Principal Component Analysis) and supervised analysis (Significance analysis of microarray). The select up-regulated and candidate miRNAs associated with monosomy 3 uveal melanoma tumors were validated further with qRT-PCR (n=86). Thus, this study indicates the role of miRNAs in UM tumor progression and their implication in predetermining the liver metastasis. The study consists of six uveal melanoma primary tumour tissues of South Asian-Indian population. These six tumours have been screened for chromosome 3 abberation using chromogenic in-situ hybridisation (CISH). Thus, samples under the study includes three each of monosomy 3 and disomy 3. The miRNA profiling were carried out from the tumor sections of formalin-fixed paraffin embedded eyeball samples. The up-regulated miRNAs associated with monosomy 3 uveal melanoma tumors were short listed and the candidate miRNAs were validated further with qRT-PCR. Agilent one-color experiment, Organism: Homo sapiens, Agilent Human miRNA 8x15k Arrays AMADID: 021827 [Agilent miRNA labeling reagent and Hybridization Kit Cat # 5190-0408]