Genome-wide CRISPR sgRNA loss-of-function screening in PRCC-TFE3 inducible HK-2 cells

Although PRCC-TFE3 can trigger either oncogene-induced senescence (OIS) or tumor progression depending on the cellular context, both phenotypes are fundamentally dependent on its transcriptional function. This study aims to identify genetic factors essential for the transcriptional activity and functional output of PRCC-TFE3.

Using a doxycycline (Dox)-inducible PRCC-TFE3 HK-2 cell model where the fusion protein induces robust OIS, we performed a genome-wide CRISPR/Cas9 knockout screen. By identifying genes whose loss alleviates this OIS phenotype, we sought to uncover key regulators required for PRCC-TFE3-mediated transcriptional programs.