Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Evaluation of microRNA expression profiles and their associations with risk alleles in lymphoblastoid cell lines of familial ovarian cancer

ABSTRACT: We evaluated the genome-wide microRNA expression profiles in lymphoblastoid cell lines of familial ovarian cancer patients and controls We used microarray to perform microRNA profiling in lymphoblastoid cell lines from 74 women with familial ovarian cancer patients and 47 controls.

ORGANISM(S): Homo sapiens

SUBMITTER: Dan Wang

PROVIDER: E-GEOD-31801 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Evaluation of microRNA expression profiles and their associations with risk alleles in lymphoblastoid cell lines of familial ovarian cancer.

Shen Jie J Wang Dan D Gregory Steven R SR Medico Leonard L Hu Qiang Q Yan Li L Odunsi Kunle K Lele Shashikant B SB Ambrosone Christine B CB Liu Song S Zhao Hua H

Carcinogenesis 20120110 3

Interindividual variations of microRNA expression are likely to influence the expression of microRNA target genes and, therefore, contribute to phenotypic differences in humans, including cancer susceptibility. Whether microRNA expression variation has any role in ovarian cancer development is still unknown. Here, we evaluated microRNA expression profiles in lymphoblastoid cell lines from 74 women with familial ovarian cancer and 47 unrelated controls matched on gender and race. We found that th ...[more]

PMID: 22235027

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Project description:Abstract: Background & Aims: Unusual hypervascularity is a hallmark of human hepatocellular carcinoma (HCC). Although microRNA-214 (miR-214) is upregulated in other human cancers, it is downregulated in HCC. We elucidated the biological and clinical significance of miR-214 downregulation in HCC. Methods: MicroRNAs deregulated in HCC were identified using array-based MicroRNA profiling. A luciferase reporter assay confirmed target association between miR-214 and hepatoma-derived growth factor (HDGF). Tube formation and in vivo angiogenesis assays validated the roles of miR-214/HDGF in angiogenesis. Results: MiR-214 downregulation was associated with higher tumor recurrence and worse clinical outcomes. Ectopic expression of miR-214 suppressed xenograft tumor growth and microvascularity of the tumor and its surrounding tissues. The genes downregulated by ectopic expression of miR-214 were involved in the regulation of apoptosis, cell cycle, and angiogenesis. Integrated analysis disclosed HDGF as a downstream target of miR-214. Conditioned medium of HCC cells contained bioactivity to stimulate tube formation of human umbilical vein endothelial cells, which was abolished by pretreatment of the conditioned media with HDGF antibodies, silencing of HDGF expression or ectopic expression of miR-214 in the donor HCC cells. The angiogenic activity of the conditioned media lost by ectopic expression of miR-214 in the donor cells was restored by supplementation with recombinant HDGF. In vivo tumor angiogenesis assays showed significant suppression of tumor vascularity by ectopic expression of miR-214. Conclusions: A novel role of microRNA in tumrigenesis is identified. Downregulation of miR-214 contributes to unusual hypervascularity of HCC via activation of the HDGF paracrine pathway for tumor angiogenesis. To identify miRNAs that are deregulated in human HCC, 68 HCC and 21 non-tumor liver tissues were subjected to profiling of miRNA expression using miRNA arrays containing 739 human miRNA probes. Differentially expressed microRNAs were identified.

Dataset Information

Evaluation of microRNA expression profiles and their associations with risk alleles in lymphoblastoid cell lines of familial ovarian cancer

Publications

Evaluation of microRNA expression profiles and their associations with risk alleles in lymphoblastoid cell lines of familial ovarian cancer.

Similar Datasets

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