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• W2944177549 abstract "Summary We report that the oncogenic transcription factor FOXM1 is arranged in a head-to-head configuration with RHNO1 , a gene involved in the ATR/CHK1-dependent DNA replication stress (DRS) response. FOXM1 and RHNO1 are both amplified and upregulated in high-grade serous ovarian cancer (HGSC). FOXM1 and RHNO1 expression are closely associated in normal and cancer tissues, including single cells, and a bidirectional promoter (F/R-BDP) mediates balanced expression. Targeting of FOXM1 and RHNO1 in HGSC cells using shRNA, CRISPR mutagenesis, or CRISPR interference directed to the F/R-BDP reduced DNA homologous recombination repair (HR) capacity, increased DNA damage, reduced clonogenic survival, and sensitized HGSC cells to the poly-ADP ribosylase inhibitor (PARPi) olaparib. Thus, there is functional cooperativity between FOXM1 and RHNO1 in cancer cells, and combinatorial targeting of this bidirectional gene pair may be a novel cancer therapeutic strategy. More broadly, our data provide evidence that bidirectional gene units function in human cancer." @default.
• W2944177549 created "2019-05-16" @default.
• W2944177549 creator A5008389256 @default.
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• W2944177549 date "2019-05-07" @default.
• W2944177549 modified "2023-09-23" @default.
• W2944177549 title "Co-regulation and functional cooperativity of FOXM1 and RHNO1 bidirectional genes in ovarian cancer" @default.
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• W2944177549 doi "https://doi.org/10.1101/630442" @default.
• W2944177549 hasPublicationYear "2019" @default.
• W2944177549 type Work @default.
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