Identification of thyroid tumor cell vulnerabilities through a siRNA-based functional screening

Maria Chiara Anania, Fabio Gasparri, Elena Cetti, Ivan Fraietta, Katia Todoerti, Claudia Miranda, Mara Mazzoni, Claudia Re, Riccardo Colombo, Giorgio Ukmar, Stefano Camisasca, Sonia Pagliardini, Marco A. Pierotti, Antonino Neri, Arturo Galvani, Angela Greco

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)34629-34648
Number of pages20
JournalOncotarget
Volume6
Issue number33
DOIs
Publication statusPublished - 2015

Keywords

  • COPZ1
  • Cyclin D1
  • MASTL
  • Non-oncogene addiction
  • Thyroid cancer

ASJC Scopus subject areas

  • Oncology

Fingerprint

Dive into the research topics of 'Identification of thyroid tumor cell vulnerabilities through a siRNA-based functional screening'. Together they form a unique fingerprint.

Cite this