Tumor suppressive activities for pogo transposable element derived with KRAB domain via ribosome biogenesis restriction [RNA-seq]
Transposable elements play indispensable roles in human development, contributing significantly to pluripotency and embryogenesis. However, Transposable elements sequences also play a role in human pathologies, particularly cancer, where they function as cis/transcriptional regulators, produce non-coding RNAs, and act as mutagens disrupting tumor suppressors. Despite this understanding, the involvement of Transposable elements-derived genes in tumor pathogenesis remains poorly understood. In this study, we conducted systematic analyses of TEG expression across various human cancers, highlighting the significant role of POGK. Our findings demonstrate that POGK functions as a tumor suppressor in TNBC. We found that POGK globally inhibits ribosomal gene expression using RNA-Seq. Furthermore, we reveal that POGK interacts with the co-repressor TRIM28 to directly block the transcription of ribosomal genes RPS16 and RPS29 through ChIP-Seq data, thereby leading to widespread inhibition of ribosomal biogenesis. Crucially, our findings reveal that POGK is deactivated through isoform switching in clinical TNBC. This discovery sheds new light on its previously unidentified and repurposed roles in regulating tumor growth. Overall design: To identify genes regulated by POGK, we analyzed the gene expression profiles of POGK-overexpressing stable cells compared to control cells in the SUM159 cell line using HISEQ.