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 +9 more
Reads0
Chats0
TLDR
This paper showed that RHNO1 and FOXM1 are head-to-head (i.e., bidirectional) genes (BDG) regulated by a BDP (named F/R-BDP), which is a potential therapeutic approach for ovarian and other cancers.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.read more
Citations
More filters
Journal ArticleDOI
Human NLRP1 is a sensor of pathogenic coronavirus 3CL proteases in lung epithelial cells
Rémi Planès,Miriam Pinilla,Karin Santoni,Audrey Hessel,Charlotte Passemar,Kenneth James Lay,P. Paillette,Ana Luiza Chaves Valadão,Kim S. Robinson,Paul Bastard,Nathan Lam,Ricardo Fadrique,Ida Rossi,David Péricat,Salimata Bagayoko,Stephen A. Leon-Icaza,Yoann Rombouts,Eric Perouzel,M Tiraby,Qian Zhang,Pietro Cicuta,Emmanuelle Jouanguy,Olivier Neyrolles,Clare E. Bryant,Andres Floto,Caroline Goujon,Franklin Zhong Lei,Guillaume Martin-Blondel,Stein Silva,Jean-Laurent Casanova,Céline Cougoule,Bruno Reversade,Julien Marcoux,Emmanuel Ravet,Etienne Meunier +34 more
TL;DR: In this article , the authors identify the NLRP1 inflammasome as a sensor of SARS-CoV-2 infection in lung epithelia and demonstrate that 3CL proteases also inactivate the pyroptosis executioner Gasdermin D (GSDMD).
Journal ArticleDOI
FOXM1: A Multifunctional Oncoprotein and Emerging Therapeutic Target in Ovarian Cancer.
TL;DR: Forkhead box M1 (FOXM1) is a member of the conserved forkhead box (FOX) transcription factor family and has been shown to promote critical oncogenic phenotypes in ovarian cancer, including cell proliferation, invasion and metastasis, chemotherapy resistance, cancer stem cell (CSC) properties, genomic instability and altered cellular metabolism as discussed by the authors.
Journal ArticleDOI
The Pan-Cancer Multi-Omics Landscape of FOXO Family Relevant to Clinical Outcome and Drug Resistance
Jindong Xie,Junsheng Zhang,Wenwen Tian,Yu-chao Zou,Yu-Chien Tang,Shaoquan Zheng,Chau Wei Wong,Xinpei Deng,Song Wu,Junxin Chen,Yunxian Mo,Xiaolin Xie +11 more
TL;DR: In this article , the authors evaluated the expression, prognostic value, mutation, methylation, and clinical features of four FOXO family genes (FOXO1, FOXO3,FOXO4, and FOXO6) in 33 types of cancers based on the Cancer Genome Atlas (TCGA) and Genotype Tissue Expression (GTEx) databases.
Journal ArticleDOI
Spirocyclic dimer SpiD7 activates the unfolded protein response to selectively inhibit growth and induce apoptosis of cancer cells
Smit Kour,Sandeep Kumar Rana,S. Kubica,Smitha Kizhake,Mudassier Ahmad,Catalina Munoz-Trujillo,David Klinkebiel,Sarbjit Singh,Jayapal Reddy Mallareddy,Surabhi Chandra,Nicholas T. Woods,Adam R. Karpf,Amarnath Natarajan +12 more
TL;DR: In this article , a spirocyclic dimer, SpiD7, was identified and evaluated its effects on UPR activation signals, that is, XBP1 splicing, phosphorylation of eIF2α, and a decrease in ATF 6 levels, in normal and cancer cells, which were further confirmed by RNA-Seq analyses.
Journal ArticleDOI
SOCS7/HuR/FOXM1 signaling axis inhibited high-grade serous ovarian carcinoma progression
TL;DR: In this article , the authors investigated the functions and mechanisms of suppressors of cytokine signaling 7 (SOCS7) in HGSOC and found that SOCS7 acted as a suppressor by inhibiting cancer cell viability and tumor growth in vivo.
References
More filters
Journal ArticleDOI
Targeting of mutant p53-induced FoxM1 with thiostrepton induces cytotoxicity and enhances carboplatin sensitivity in cancer cells
TL;DR: Novel evidence is provided that both amorphic and neomorphic mutations in TP53 contribute to FoxM1 overexpression and that FoxM 1 may be targeted for therapeutic benefits in cancers.
Journal ArticleDOI
Transcription factor FoxM1 is the downstream target of c-Myc and contributes to the development of prostate cancer
TL;DR: FoxM1 was significantly increased in prostate cancer samples, and it could regulate the proliferative and invasive ability of prostate cancer cells which might be a new target for prostate cancer.
Journal ArticleDOI
FoxM1 Promotes Cell Proliferation, Invasion, and Stem Cell Properties in Nasopharyngeal Carcinoma.
TL;DR: FoxM1 greatly induces cancer progression and cancer stem cell (CSC) features in NPC and enhanced the ability of tumourigenicity of NPC cell lines in mice xenograft.
Journal ArticleDOI
Olaparib-induced Adaptive Response Is Disrupted by FOXM1 Targeting that Enhances Sensitivity to PARP Inhibition.
TL;DR: It is demonstrated thatFOXM1 plays an important role in the adaptive response induced by olaparib and FOXM1 inhibition by thiostrepton induces “BRCAness” and enhances sensitivity to PARP inhibitors.
Journal ArticleDOI
Copy Number Amplification of DNA Damage Repair Pathways Potentiates Therapeutic Resistance in Cancer.
Zhiyuan Wu,Zhiyuan Wu,Sihan Li,Xuemei Tang,Yue Wang,Weiwei Guo,Guojun Cao,Kun Chen,Min Zhang,Ming Guan,Da Yang +10 more
TL;DR: DDR gene amplification can lead to chemotherapy resistance and poor overall survival by augmenting DDR, and these amplified DDR genes may serve as actionable clinical biomarkers for cancer management.