論文 - 詳細
| RRC ID | 67258 |
|---|---|
| 著者 | Anania M, Gasparri F, Cetti E, Fraietta I, Todoerti K, Miranda C, Mazzoni M, Re C, Colombo R, Ukmar G, Camisasca S, Pagliardini S, Pierotti M, Neri A, Galvani A, Greco A. |
| タイトル | Identification of thyroid tumor cell vulnerabilities through a siRNA-based functional screening. |
| ジャーナル | Oncotarget |
| Abstract |
The incidence of thyroid carcinoma is rapidly increasing. Although generally associated with good prognosis, a fraction of thyroid tumors are not cured by standard therapy and progress to aggressive forms for which no effective treatments are currently available. In order to identify novel therapeutic targets for thyroid carcinoma, we focused on the discovery of genes essential for sustaining the oncogenic phenotype of thyroid tumor cells, but not required to the same degree for the viability of normal cells (non-oncogene addiction paradigm). We screened a siRNA oligonucleotide library targeting the human druggable genome in thyroid cancer BCPAP cell line in comparison with immortalized normal human thyrocytes (Nthy-ori 3-1). We identified a panel of hit genes whose silencing interferes with the growth of tumor cells, while sparing that of normal ones. Further analysis of three selected hit genes, namely Cyclin D1, MASTL and COPZ1, showed that they represent common vulnerabilities for thyroid tumor cells, as their inhibition reduced the viability of several thyroid tumor cell lines, regardless the histotype or oncogenic lesion. This work identified non-oncogenes essential for sustaining the phenotype of thyroid tumor cells, but not of normal cells, thus suggesting that they might represent promising targets for new therapeutic strategies. |
| 巻・号 | 6(33) |
| ページ | 34629-48 |
| 公開日 | 2015-10-27 |
| DOI | 10.18632/oncotarget.5282 |
| PII | 5282 |
| PMID | 26431489 |
| PMC | PMC4741478 |
| MeSH | Blotting, Western Carcinoma / genetics* Carcinoma / pathology Carcinoma, Papillary Cell Line, Tumor Cell Proliferation / genetics Coatomer Protein / genetics* Fluorescent Antibody Technique Gene Expression Profiling / methods Genes, bcl-1 / genetics* High-Throughput Nucleotide Sequencing / methods* Humans Microtubule-Associated Proteins / genetics* Polymerase Chain Reaction Protein Serine-Threonine Kinases / genetics* RNA, Small Interfering Sequence Analysis, RNA / methods Thyroid Cancer, Papillary Thyroid Neoplasms / genetics* Thyroid Neoplasms / pathology Transcriptome Transfection |
| IF | 5.168 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 各媒体での言及数の合計 | 0 |
| リソース情報 | |
| ヒト・動物細胞 | HTC/C3(RCB0452) |