1. Co-regulation and function of FOXM1 / RHNO1 bidirectional genes in cancer.
- Author
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Barger CJ, Chee L, Albahrani M, Munoz-Trujillo C, Boghean L, Branick C, Odunsi K, Drapkin R, Zou L, and Karpf AR
- Subjects
- Ataxia Telangiectasia Mutated Proteins genetics, Ataxia Telangiectasia Mutated Proteins metabolism, Carboplatin pharmacology, Carrier Proteins metabolism, Cell Line, Tumor, Cell Proliferation, Checkpoint Kinase 1 genetics, Checkpoint Kinase 1 metabolism, Databases, Genetic, Drug Resistance, Neoplasm, Female, Forkhead Box Protein M1 metabolism, Humans, Neoplasms, Cystic, Mucinous, and Serous drug therapy, Neoplasms, Cystic, Mucinous, and Serous metabolism, Neoplasms, Cystic, Mucinous, and Serous pathology, Ovarian Neoplasms drug therapy, Ovarian Neoplasms metabolism, Ovarian Neoplasms pathology, Poly(ADP-ribose) Polymerase Inhibitors pharmacology, Promoter Regions, Genetic, Recombinational DNA Repair, Signal Transduction, Carrier Proteins genetics, Forkhead Box Protein M1 genetics, Gene Expression Regulation, Neoplastic, Neoplasms, Cystic, Mucinous, and Serous genetics, Ovarian Neoplasms genetics
- 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 co-expressed 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., Competing Interests: CB, LC, MA, CM, LB, CB, KO, RD, LZ, AK No competing interests declared, (© 2021, Barger et al.)
- Published
- 2021
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