| Title |
Thymic Epithelial Tumors phenotype relies on miR-145-5p epigenetic regulation
|
|---|---|
| Published in |
Molecular Cancer, May 2017
|
| DOI | 10.1186/s12943-017-0655-2 |
| Pubmed ID | |
| Authors |
Teresa Bellissimo, Federica Ganci, Enzo Gallo, Andrea Sacconi, Claudia Tito, Luciana De Angelis, Claudio Pulito, Silvia Masciarelli, Daniele Diso, Marco Anile, Vincenzo Petrozza, Felice Giangaspero, Edoardo Pescarmona, Francesco Facciolo, Federico Venuta, Mirella Marino, Giovanni Blandino, Francesco Fazi |
| Abstract |
Thymoma and thymic carcinoma are the most frequent subtypes of thymic epithelial tumors (TETs). A relevant advance in TET management could derive from a deeper molecular characterization of these neoplasms. We previously identified a set of microRNA (miRNAs) differentially expressed in TETs and normal thymic tissues and among the most significantly deregulated we described the down-regulation of miR-145-5p in TET. Here we describe the mRNAs diversely regulated in TETs and analyze the correlation between these and the miRNAs previously identified, focusing in particular on miR-145-5p. Then, we examine the functional role of miR-145-5p in TETs and its epigenetic transcriptional regulation. mRNAs expression profiling of a cohort of fresh frozen TETs and normal tissues was performed by microarray analysis. MiR-145-5p role in TETs was evaluated in vitro, modulating its expression in a Thymic Carcinoma (TC1889) cell line. Epigenetic transcriptional regulation of miR-145-5p was examined by treating the TC1889 cell line with the HDAC inhibitor Valproic Acid (VPA). Starting from the identification of a 69-gene signature of miR-145-5p putative target mRNAs, whose expression was inversely correlated to that of miR-145-5p, we followed the expression of some of them in vitro upon overexpression of miR-145-5p; we observed that this resulted in the down-regulation of the target genes, impacting on TETs cancerous phenotype. We also found that VPA treatment of TC1889 cells led to miR-145-5p up-regulation and concomitant down-regulation of miR-145-5p target genes and exhibited antitumor effects, as indicated by the induction of cell cycle arrest and by the reduction of cell viability, colony forming ability and migration capability. The importance of miR-145-5p up-regulation mediated by VPA is evidenced by the fact that hampering miR-145-5p activity by a LNA inhibitor reduced the impact of VPA treatment on cell viability and colony forming ability of TET cells. Finally, we observed that VPA was also able to enhance the response of TET cells to cisplatin and erlotinib. Altogether our results suggest that the epigenetic regulation of miR-145-5p expression, as well as the modulation of its functional targets, could be relevant players in tumor progression and treatment response in TETs. |
X Demographics
The data shown below were collected from the profile of 1 X user who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 28 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 28 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 5 | 18% |
| Other | 3 | 11% |
| Student > Master | 3 | 11% |
| Student > Bachelor | 2 | 7% |
| Student > Postgraduate | 2 | 7% |
| Other | 3 | 11% |
| Unknown | 10 | 36% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 10 | 36% |
| Biochemistry, Genetics and Molecular Biology | 6 | 21% |
| Agricultural and Biological Sciences | 2 | 7% |
| Chemical Engineering | 1 | 4% |
| Immunology and Microbiology | 1 | 4% |
| Other | 1 | 4% |
| Unknown | 7 | 25% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 11 May 2017.
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#20,420,242
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#1,485
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#270,553
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Outputs of similar age from Molecular Cancer
#22
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