| Experiment ID | EXP00274 |
| Reference | Title: MicroRNA-375/SEC23A as biomarkers of the in vitro efficacy of vandetanib. Author: Lassalle S, Zangari J, Popa A, IlieM, Hofman V, Long E,Patey M, Tissier F, Belléannée G, Trouette H, Catargi B,Peyrottes I, Sadoul JL, Bordone O, Bonnetaud C, Butori C, Bozec A, Guevara N, Santini J, Hénaoui IS, Lemaire G, Blank O, Vielh P, Barbry P, MariB, Brest P, Hofman P. Journal: Oncotarget. 2016 Mar 29. doi: 10.18632/oncotarget.8458. [Epub ahead of print] Abstract: In this study, we performed microRNA (miRNA) expression profiling on a largeseries of sporadic and hereditary forms of medullary thyroid carcinomas (MTC).More than 60 miRNAs were significantly deregulated in tumor vs adjacent non-tumortissues, partially overlapping with results of previous studies. We focused ourattention on the strongest up-regulated miRNA in MTC samples, miR-375, thederegulation of which has been previously observed in a variety of humanmalignancies including MTC. We identified miR-375 targets by combining geneexpression signatures from human MTC (TT) and normal follicular (Nthy-ori 3-1)cell lines transfected with an antagomiR-375 inhibitor or a miR-375 mimic,respectively, and from an in silico analysis of thyroid cell lines of Cancer CellLine Encyclopedia datasets. This approach identified SEC23A as a bona fidemiR-375 target, which we validated by immunoblotting and immunohistochemistry of non-tumor and pathological thyroid tissue. Furthermore, we observed that miR-375 overexpression was associated with decreased cell proliferation andsynergistically increased sensitivity to vandetanib, the clinically relevanttreatment of metastatic MTC. We found that miR-375 increased PARP cleavage anddecreased AKT phosphorylation, affecting both cell proliferation and viability.We confirmed these results through SEC23A direct silencing in combination withvandetanib, highlighting the importance of SEC23A in the miR-375-associatedincreased sensitivity to vandetanib.Since the combination of increased expressionof miR-375 and decreased expression of SEC23A point to sensitivity to vandetanib,we question if the expression levels of miR-375 and SEC23A should be evaluated asan indicator of eligibility for treatment of MTC patients with vandetanib. PMID: 27036030 |
| Expressiion Profile | Description: MiRNA expression profiling in human medullary thyroid carcinoma Organism: Homo sapiens GEO ID: GSE40807 Platform: GPL8227 Number of samples: 80 |
| Design and Sample | Cancer Type: thyroid cancer Cancer SubType: N/D Cell Line: N/D Experimental Design: cancer vs normal Case Sample: thyroid cancer Control Sample: normal tissue Num of Case: 40 Num of Control: 40 Quantification Software: Limma Num of miRNAs: 719 |
| Identification | Num of Up: 95 Num of Down: 80 |