Identification of synthetic lethality of PRKDC in MYC-dependent human cancers by pooled shRNA screening.

ABSTRACT:

Background

MYC family members are among the most frequently deregulated oncogenes in human cancers, yet direct therapeutic targeting of MYC in cancer has been challenging thus far. Synthetic lethality provides an opportunity for therapeutic intervention of MYC-driven cancers.

Methods

A pooled kinase shRNA library screen was performed and next-generation deep sequencing efforts identified that PRKDC was synthetically lethal in cells overexpressing MYC. Genes and proteins of interest were knocked down or inhibited using RNAi technology and small molecule inhibitors, respectively. Quantitative RT-PCR using TaqMan probes examined mRNA expression levels and cell viability was assessed using CellTiter-Glo (Promega). Western blotting was performed to monitor different protein level

SUBMITTER: Zhou Z 

PROVIDER: S-EPMC4320452 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature