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

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. 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.