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- Title
Co-regulation and function of FOXM1/ RHNO1 bidirectional genes in cancer.
- Authors
Barger, Carter J.; Chee, Linda; Albahrani, Mustafa; Munoz-Trujillo, Catalina; Boghean, Lidia; Branick, Connor; Odunsi, Kunle; Drapkin, Ronny; Zou, Lee; Karpf, Adam R.
- 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 FOXM1 is co-amplified and coexpressed with RHNO1, a gene involved in the ATR-Chk1 signaling pathway that functions in the DNA replication stress response. We demonstrate that FOXM1 and RHNO1 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.
- Subjects
CANCER genes; POLY ADP ribose; THERAPEUTICS; RECOMBINANT DNA; DNA replication; PHENOTYPES
- Publication
eLife, 2021, p1
- ISSN
2050-084X
- Publication type
Article
- DOI
10.7554/eLife.55070