Transcriptomics,Genomics

Dataset Information

19

Overexpression of microRNA-375 in medullary thyroid carcinoma cells hinders cell proliferation and improves the vandetanib efficacy effect in vitro


ABSTRACT: The global microRNA (miRNA) profiling expression was assessed in a large series of both sporadic and hereditary forms of medullary thyroid carcinomas (MTC), and to evaluate the biological function of major found altered miRNAs. For this purpose we investigated miRNA differential expression in tumoral vs adjacent non tumoral tissues from 62 MTC patients, and showed a specific overexpression of miR-375, -129-3p, -376c, -335, -96, -10a, -7, -429 and an underexpression of miR-451 in tumoral tissues. Since miR-375 was the most up-regulated miRNA, we thus decided to identify its targets by combining a transcriptomic signature of cells transfected either with premiR- or antagomiR-375 and an in silico analysis joining TT-cells mRNA specific signature from Cancer Cell Line Encyclopedia GEO dataset and miRNA prediction algorithms. Using this restrictive approach, we focused on miR-375 target SEC23A and validated a decreased expression of SEC23A by Western blotting and by immunohistochemistry in tumoral vs non tumoral adjacent thyroid epithelium. Furthermore, we observed that overexpression of miR-375 was associated with decreased proliferation and increased vandetanib response in vitro. Overall, our results showed an overexpression of miR-375 in MTC in association with a decrease of miR-375-potential targets including SEC23A. Additionnally, we postulate thatmiR-375 overexpression should be evaluated in MTC patients treated with the tyrosine kinase inhibitor, vandetanib. Overall design: 2 cell lines: TT and ORI (Nthy ORI 3.1) transfected with the antagomir-375 and premir-375 respectively. For each condition a control condition was provided. A total of 4 conditions: 2 transfections and their 2 respective controls are analyzed. For each condition 2 replica are provided. A total of 8 samples are submitted in this dataset.

INSTRUMENT(S): Agilent-039494 SurePrint G3 Human GE v2 8x60K Microarray 039381 (Feature Number version)

SUBMITTER: Kevin Lebrigand  

PROVIDER: GSE67742 | GEO | 2016-05-22

SECONDARY ACCESSION(S): PRJNA280808

REPOSITORIES: GEO

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In this study, we performed microRNA (miRNA) expression profiling on a large series of sporadic and hereditary forms of medullary thyroid carcinomas (MTC). More than 60 miRNAs were significantly deregulated in tumor vs adjacent non-tumor tissues, partially overlapping with results of previous studies. We focused our attention on the strongest up-regulated miRNA in MTC samples, miR-375, the deregulation of which has been previously observed in a variety of human malignancies including MTC. We ide  ...[more]

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