ABSTRACT: Overexpression of microRNA-375 in medullary thyroid carcinoma cells hinders cell proliferation and improves the vandetanib efficacy effect in vitro
Project description: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.
Project description:To identify a microRNA profile of human medullary thyroid cancer (MTC), we performed a miRNA microarray analysis exploiting 8 primary tumours and 9 paired neck nodes metastases in comparison with 3 non-neoplastic thyroid tissues.
Project description:<p>In this study, patients with advanced cancer across all histologies were enrolled in our IRB approved clinical sequencing program, called MI-ONCOSEQ, to go through an integrative sequencing which includes whole exome sequencing of the tumor and matched normal, and transcriptome sequencing. Four index cases were identified which harbor gene rearrangements of FGFR2 including two cholangiocarcinoma cases, a metastatic breast cancer case, and a metastatic prostate cancer case. After extending our assessment of FGFR rearrangements across multiple tumor cohorts, including TCGA, we identified FGFR gene fusions with intact kinase domains of FGFR1, FGFR2, or FGFR3 in cholangiocarcinoma, breast cancer, prostate cancer, lung squamous cell cancer, bladder cancer, thyroid cancer, oral cancer, glioblastoma, and head and neck squamous cell cancer. All FGFR fusion partners tested exhibit oligomerization capability, suggesting a shared mode of kinase activation. Overexpression of FGFR fusion proteins in vitro induced cell proliferation, and bladder cancer cell lines that harbors FGFR3 fusion proteins exhibited enhanced susceptibility to pharmacologic inhibition in vitro and in vivo. Due to the combinatorial possibilities of FGFR family fusion to a variety of oligomerization partners, clinical sequencing efforts which incorporate transcriptome analysis for gene fusions are poised to identify rare, targetable FGFR fusions across diverse cancer types.</p>
Project description:This study aims to investigate the microRNA profile in human medullary carcinoma tissue by microarray analysis and RT-qPCR. Matched tumor and adjacent normal tissue were obtained from 24 patients and analysed using human microRNA Microarray Kit Agilent, Differentially expressed miRNAs were validated by RT-qPCR using 37 other tumors samples (validation set), Associations of microRNA expression with clinicopathological items were studied Matched tumor and adjacent normal frozen tissues were obtained from thyroid of 40 patients. Normal tissue (name with suffix S) and lesionnal tissue (name with suffix L) were hybridized on microarray.
Project description:Transcriptional analysis of 49 primary medullary thyroid carcinoma tumors. Comparisons MTCM918T vs MTC634 and MTCM918T vs MTCWT. 49 (52 hybridized tumors with 3 replicates) primary Medullary Thyroid Carcinoma (MTC) cases were hybridized onto a cDNA microarray in order to identify the unique markers for specific genetic classes of MTC.
Project description:The oligo microarrays were used to determine microRNA expression profiles of medullary thymic epithelial cells (mTECs) submitted of in vitro Aire Knockdown (siRNA silencing).
Project description:The aim of the study was to identify major gene expression changes associated to sunitinib response in a human medullary thyroid carcinoma (MTC)ﾠmodel.ﾠWe developed an in vitro kinetic microarray study. The humanﾠﾠMTC cell line, the TT cells, were treated with 250 nM sunitinib or vehicle during 1, 3 and 6 days. Total mRNA from sunitinib treated cells were compared to placebo treated ones for each time point.
