Co-regulation and function of < i > FOXM1 < /i > / < i > RHNO1 < /i > bidirectional genes in cancer

The FOXM1 transcription factor is an oncoprotein and a top biomarker of poor prognosis in human cancer. Overexpression and activation of FOXM1 is frequent in high-grade serous carcinoma (HGSC), the most common and lethal form of human ovarian cancer, and is linked to copy number gains at chromosome 12p13.33. We show thatFOXM1 is co-amplified and co-expressed withRHNO1, a gene involved in the ATR-Chk1 signaling pathway that functions in the DNA replication stress (RS) response. We demonstrate thatFOXM1 andRHNO1 are head-to-head (i.e. bidirectional) genes (BDG) regulated by a bidirectional promoter (BDP) (named F/R-BDP). FOXM1 and RHNO1 each promote oncogenic phenotypes in HGSC cells, including clonogenic growth, DNA homologous recombination repair (HR), and poly-ADP ribosylase (PARP) inhibitor resistance. FOXM1 and RHNO1 are one of the first examples of oncogenic BDG, and therapeutic targeting of FOXM1/RHNO1 BDG is a potential therapeutic approach for ovarian and other cancers.
Source: eLife - Category: Biomedical Science Tags: Cancer Biology Chromosomes and Gene Expression Source Type: research