Unknown,Transcriptomics,Genomics,Proteomics

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MicroRNA Dysregulation in Human Prostate Cancer Cell Model (M12 and P69)

ABSTRACT: An isogenic prostate cancer cell model was used to profile miRNA changes that contribute to the tumorigenic state of prostate cancer. P69 cells are an SV40 large T antigen immortalized cell line that is poorly tumorigenic and non-metastatic. The M12 derivative was derived from an in vivo selection process using nude, athymic mice. Immortalized cells were cultured and used to extract RNA and probed against the human miRNA panel from Exiqon. There were a total of 186 miRNAs that were at least two fold differentially regulated . Two human prostate cancer cell lines were used to evaluate miRNA expression differences contributing to oncogenesis. Two replicates were performed and the data presented as the mean fold difference between P69 and M12.

ORGANISM(S): Homo sapiens

SUBMITTER: William Budd

PROVIDER: E-GEOD-49520 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Osteoporosis is the consequence of altered bone metabolism resulting in the systemic reduction of bone strength and increased risk of fragility fractures. MicroRNAs (miRNAs) regulate gene expression on a post-transcriptional level are known to take part in the control of bone formation and bone resorption. Recently, targeted secretion of miRNAs from cells originating from various tissues has been described, which allows for their minimal-invasive detection in serum/plasma and use as biomarkers for presence and progression of pathological conditions. One pilot study has reported circulating miRNAs in serum and tissue of fracture patients. However, further studies are required to explore whether a dysbalance in bone homeostasis of fracture patients can reliably be reflected by specific circulating miRNAs, and whether these miRNAs might serve as drugable targets. Here, we report results from a comprehensive multiplex study of 175 miRNAs in serum samples obtained from 7 patients with osteoporotic fractures at the femoral neck, and 7 age-matched controls. Following elaborate quality control statistical analysis of this exploratory dataset identified 9 microRNAs with altered serum levels in response to fracture (adjusted p-value < 0.1). Of these, hsa-miR-10a/b gave excellent discrimination of both groups (AUC = 1.0), and clustering of samples based on the top10 miRNAs confirmed the high discriminatory power of circulating microRNAs for osteoporotic fractures. In the next step 3 miRNAs with unknown roles in osteogenic differentiation and 4 miRNA from a previous study were tested for their effects on osteogenic differentiation. Of these, 3 miRNAs showed robust effects on osteogenic differentiation. Overall, these data provide important insights into changes in serum miRNA in post-traumatic patients. Future studies will show, whether this knowledge can be used to improve current diagnostic methodologies to predict fracture risk and design novel treatment strategies for osteoporosis patients. Two groups with n=7 per group; one groups represents cases with osteoporotic fractures, the control group is age-matched without fractures