RRC ID 67258
Author 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.
Title Identification of thyroid tumor cell vulnerabilities through a siRNA-based functional screening.
Journal 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.
Volume 6(33)
Pages 34629-48
Published 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
Human and Animal Cells HTC/C3(RCB0452)