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
Human ovarian surface epithelial cells immortalized with hTERT maintain functional pRb and p53 expression
N. F. Li,S. Broad,Yong-Jie Lu,J. S. Yang,R. Watson,Thorsten Hagemann,George D. Wilbanks,George D. Wilbanks,Ian Jacobs,Frances R. Balkwill,Dimitra Dafou,Simon A. Gayther +11 more
TL;DR: This study suggests that inactivation of pRb and p53 is not necessary for OSE immortalization, and down‐regulation of p15INK4B in the immortalized cells may indicate a functional role for this protein in them.
Journal ArticleDOI
RHINO forms a stoichiometric complex with the 9-1-1 checkpoint clamp and mediates ATR-Chk1 signaling
TL;DR: It is shown that RHINO (for Rad9, Rad1, Hus1 interacting nuclear orphan) forms complexes with both the 9-1-1 checkpoint clamp and TopBP1 in human cells even in the absence of treatments with DNA damaging agents, and the loss of RHINO partially abrogates ATR-Chk1 signaling following UV irradiation.
Journal ArticleDOI
FOXM1 is a downstream target of LPA and YAP oncogenic signaling pathways in high grade serous ovarian cancer
Qipeng Fan,Qingchun Cai,Yan Xu +2 more
TL;DR: It is shown for the first time that LPA up-regulates expression of active FOXM1 splice variants in a time- and dose-dependent manner in the human EOC cell lines OVCA433, CAOV3, and OVCAR5, which provides further support for the importance of these pathways as potential therapeutic targets in EOC.
Journal ArticleDOI
FoxM1, a Forkhead Transcription Factor Is a Master Cell Cycle Regulator for Mouse Mature T Cells but Not Double Positive Thymocytes
TL;DR: Unexpectedly, loss of FoxM1 only affects a few cell cycle proteins in CD4+CD8+ thymocytes and has little effect on their sensitivity to apoptosis and the subsequent steps of T cell differentiation.
Journal ArticleDOI
PARP Inhibitors for Ovarian Cancer: Current Indications, Future Combinations, and Novel Assets in Development to Target DNA Damage Repair
TL;DR: The current indications for PARPIs in both frontline and recurrent settings, current research in combination approaches, and ongoing research on novel methods to target DNA damage response are discussed in an effort to exploit the common susceptibility to DNA damage repair in epithelial ovarian cancer and improve outcomes for patients.