Co-regulation and function of foxm1/ rhno1 bidirectional genes in cancer

Carter J. Barger, Linda Chee, Mustafa Albahrani, Catalina Munoz-Trujillo, Lidia Boghean, Connor Branick, Kunle Odunsi, Ronny Drapkin, Lee Zou, Adam R. Karpf

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Article numbere55070
JournaleLife
Volume10
DOIs
StatePublished - Apr 2021

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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