التفاصيل البيبلوغرافية
| العنوان: |
mir-129-5p and Let-7 are Down-Regulated in Carcinoid Tumors. |
| المؤلفون: |
Døssing, K., Binderup, T., Kaczkowski, B., Jacobsen, A., Winther, O., Rossing, M., Federspiel, B., Knigge, U., Kjaer, A., Friis-Hansen, L. |
| المصدر: |
Neuroendocrinology; Jul2012 Supplement, Vol. 96, p2-3, 2p |
| مصطلحات موضوعية: |
RNA, GENETIC regulation, MESSENGER RNA, GENE expression, CANCER genetics, CARCINOGENESIS, NEUROENDOCRINE tumors, METASTASIS |
| مستخلص: |
Introduction: miRNAs are small non-coding RNAs that post-transcriptionally regulate gene expression by binding to comple mentary sequences on target mRNAs and their expression is often dysregulated in cancer. Aim(s): Little is known about the carcinogenesis of the slow growing neuroendocrine tumors and we therefore wanted to characterize miRNA expression in these. Materials and methods: miRNA expression in carcinoids, metastasis and normal intestinal tissue was characterized using miRNA arrays. Changes in miRNA expression were validated by in-situ hybridization and qPCR. miR-129-Sp and let-7 was selected and further characterized by mRNA arrays on total RNA from cells transfected with either miRNA. Heatmaps identified let-7 target genes involved in metastasis, miR-129-5p and its two targets EGR1 and G3BP 1 were validated by western blot analysis and luciferase assay and further examined by growth assays with ceils transfected with miR-129-5p or siRNAs against EGR1 and G3BP1. Results: miR-129-5p is down-regulated in carcinoids and the let-7 family is reduced in metastasis. When transfected into carcinoid cells, both Let-7 and miR-129-5p inhibited their growth and miR-129-5p was shown to target EGR1 and G3BP1. Knock down of EGR1 and G3BP 1 also resulted in growth inhibition mimicking that of miR-129-5p. Conclusion: miRNA expression alters intestinal carcinoids, leading to down regulation of miR-129-5p, and the let-7 family is lost in metastasis. Both are important for growth inhibition. [ABSTRACT FROM AUTHOR] |
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