eLife (2021-04-01)

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

DOI
https://doi.org/10.7554/eLife.55070
Journal volume & issue
Vol. 10

Abstract

Read online

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.

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