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Gene expression data from human NSCLC cell line (U-1810 cells) treated with miRNA-214 antagomir or non-targeting antagomir

ABSTRACT: Prognosis of non small cell lung cancer (NSCLC) is very poor mainly because it often has metastasized to distant organs already at the time of diagnosis. Therefore biomarkers which can predict metastasis are urgently needed. miRNAs have been shown to play important roles in the regulation of different tumor cell processes including those involved in metastasis. We recently showed that miRNA-214 is linked to a radioresistant phenotype of NSCLC. Interestingly, altered miRNA-214 expression has in breast, cervical and melanoma been linked to metastasis. We therefore examined the role of miRNA-214 in the metastasis of NSCLC cells. We found that down regulation of miRNA-214 increased invasive potential of NSCLC cells and conversely, overexpression of miRNA-214 in NSCLC cells with low endogenous level of miRNA-214, decreased invasiveness. Gene expression analyses of NSCLC cells with low and high levels of miRNA-214, followed by bioinformatics analyses identified a number of target genes which were linked to metastasis including pregnancy associated plasma protein A (PAPP-A), alpha protein kinase 2 (ALPK2), cyclin-dependent kinase 6 (CDK6) and tumor necrosis-factor alpha-induced protein 3 (TNFAIP3). These targets were validated on mRNA and protein level.

ORGANISM(S): Homo sapiens

PROVIDER: GSE42749 | GEO | 2013/05/25

SECONDARY ACCESSION(S): PRJNA182995

REPOSITORIES: GEO

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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

Gene expression data from human NSCLC cell line (U-1810 cells) treated with miRNA-214 antagomir or non-targeting antagomir

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