High throughput RNAi screening identifies ID1 as a synthetic sick/lethal gene interacting with the common TP53 mutation R175H

Hiroo Imai, Shunsuke Kato, Yasuhiro Sakamoto, Yuichi Kakudo, Hideki Shimodaira, Chikashi Ishioka

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

Abstract

The TP53 mutation (R175H) is one of the most common mutations in human cancer. It is a highly attractive strategy for cancer therapy to find the genes that lead the R175H-expressing cancer cells. The aim of this study was to identify the synthetic sick/lethal gene interacting with R175H. Using lentiviral bar-coded comprehensive shRNA library and a tetracycline-inducible R175H expressed in the SF126 human glioblastoma cell line (SF126-tet-R175H), we conducted high-throughput screening to identify the candidate genes that induce synthetic sickness/lethality in R175H-expressing cells. We identified 906 candidate gene suppressions that may lead to accelerated cell growth inhibition in the presence of R175H. Inhibitor of differentiation 1 (ID1) was one of the candidate genes, and its suppression by siRNA resulted in the acceleration of growth inhibition in cell lines both transiently and endogenously expressing R175H but not in TP53 -null cell lines or other common p53 mutants (such as R273H). Flow cytometry analysis showed that ID1 suppression resulted in G1 arrest, and the arrest was accelerated by the expression of R175H. ID1 is a synthetic sick/lethal gene that interacts with R175H and is considered to be a novel molecular target for cancer therapy in R175H-expressing cells.

Original languageEnglish
Pages (from-to)1043-1050
Number of pages8
JournalOncology reports
Volume31
Issue number3
DOIs
Publication statusPublished - 2014 Mar 1

Keywords

  • Gain of function
  • ID1
  • Synthetic sickness
  • TP53 common mutation

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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