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
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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
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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.
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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
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TL;DR: It is shown that cells transactivate the mitotic gene network as they exit the S phase through a CDK1 (cyclin-dependent kinase 1)–directed FOXM1 phosphorylation switch, which couples DNA replication with mitosis and preserves genome integrity by enforcing an S/G2 checkpoint.
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The Forkhead Transcription Factor FOXM1 Controls Cell Cycle-Dependent Gene Expression through an Atypical Chromatin Binding Mechanism
Xi Chen,Gerd A. Müller,Marianne Quaas,Martin Fischer,Namshik Han,Benjamin Stutchbury,Andrew D. Sharrocks,Kurt Engeland +7 more
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