Co-regulation and function of <i>FOXM1</i>/<i>RHNO1</i> bidirectional genes in cancer.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 33890574.
- Also identified by DOI 10.7554/eLife.55070 and PMC identifier 8104967.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
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 that <i>FOXM1</i> is co-amplified and co-expressed with <i>RHNO1</i>, a gene involved in the ATR-Chk1 signaling pathway that functions in the DNA replication stress response. We demonstrate that <i>FOXM1</i> and <i>RHNO1</i> 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, and poly-ADP ribosylase 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.
Medical subject headings
- Carrier Proteins
- Forkhead Box Protein M1
- Gene Expression Regulation, Neoplastic
- Neoplasms, Cystic, Mucinous, and Serous
- Ovarian Neoplasms