FBL promotes cancer cell resistance to DNA damage by transcriptionally regulating BRCA1 via YBX1

ABSTRACT: Abstract Fibrillarin (FBL) is a highly conserved nucleolar methyltransferase responsible for methylation of ribosomal RNA and proteins. In this study, we investigated the role of FBL in DNA damage response and its impact on cancer proliferation and sensitivity to DNA damaging agents. Our findings reveal that FBL is highly expressed in various cancers and is associated with poor survival outcomes in cancer patients. Knockdown of FBL sensitizes tumor cells and xenografts to DNA crosslinking agents, leading to HR-mediated DNA repair defects. We also identify Y-box binding protein-1 (YBX1) as a key interacting partner of FBL. FBL promotes the nuclear accumulation of YBX1 in response to DNA damage by enhancing the interaction between FBL and YBX1. Furthermore, we demonstrate that FBL regulates the expression of BRCA1 by modulating the binding of YBX1 to the BRCA1 promoter. Our study sheds light on the regulatory mechanism of FBL in tumorigenesis and DNA damage response, providing potential therapeutic targets to overcome chemoresistance in cancer.

ORGANISM(S): Homo sapiens (human)

SUBMITTER:  

PROVIDER: S-BSST1086 | biostudies-other |

REPOSITORIES: biostudies-other