Evidence map›Paper›PMID 39484607›Full record

ArticlebioRxiv : the preprint server for biology2024

ZNFX1 is a Novel Master Regulator in Epigenetically-induced Pathogen Mimicry and Inflammasome Signaling in Cancer.

Lora Stojanovic, Rachel Abbotts, Kaushlendra Tripathi, Collin M Coon, Saranya Rajendran, Elnaz Abbasi Farid, Galen Hostetter, Joseph W Guarnieri, Douglas C Wallace, Sheng Liu and 21 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

31 authors.

Lora StojanovicUniversity of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center, Baltimore, MD 21201, USA.
Rachel AbbottsUniversity of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center, Baltimore, MD 21201, USA.
Kaushlendra TripathiUniversity of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center, Baltimore, MD 21201, USA.
Collin M CoonMedical Sciences Program, Indiana University School of Medicine-Bloomington, Bloomington, IN 47405, USA.
Saranya RajendranMedical Sciences Program, Indiana University School of Medicine-Bloomington, Bloomington, IN 47405, USA.
Elnaz Abbasi FaridMedical Sciences Program, Indiana University School of Medicine-Bloomington, Bloomington, IN 47405, USA.
Galen HostetterVan Andel Research Institute, Grand Rapids, MI 49503, USA.
Joseph W GuarnieriCenter for Mitochondrial and Epigenomic Medicine, Division of Human Genetics, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Douglas C WallaceCenter for Mitochondrial and Epigenomic Medicine, Division of Human Genetics, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Sheng LiuDepartment of Medical and Molecular Genetics, Indiana University School of Medicine Indianapolis, IN 46202, USA.
Jun WanDepartment of Medical and Molecular Genetics, Indiana University School of Medicine Indianapolis, IN 46202, USA.
Gennaro CalendoCoriell Institute for Medical Research, Camden, NJ 08103.
Rebecca MarkerDivision of Translational Radiation Sciences, Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Zahra GohariUniversity of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center, Baltimore, MD 21201, USA.
Mohammed M A InayatullahUniversity of Southern Denmark, Odense, Denmark.
Vijay K TiwariUniversity of Southern Denmark, Odense, Denmark.
Tanjina KaderLaboratory of Systems Pharmacology, Harvard Medical School, Boston, MA, USA.
Sandro SantagataLaboratory of Systems Pharmacology, Harvard Medical School, Boston, MA, USA.
Ronny DrapkinPenn Ovarian Cancer Research Center, Department of Obstetrics and Gynecology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
Stefan KommossDiakonie-Klinikum Schwäbisch Hall, Germany, Institute for Health Informatics.
Jacobus PfistererDepartment of Medicine, David Geffen School of Medicine.
Gottfried E KonecnyUniversity of California Los Angeles, Los Angeles, CA.
Ryan CoopergardInstitute for Health Informatics, University of Minnesota, Minneapolis, MN 55455, USA.
Jean-Pierre IssaCoriell Institute for Medical Research, Camden, NJ 08103.
Boris J N WinterhoffDepartment of Obstetrics, Gynecology and Women's Health (OBGYN), Division of Gynecologic Oncology, University of Minnesota, MN 55812-3011, USA.
Michael J TopperDepartment of Oncology, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21231, USA.
George E SanduskyPathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Kathy D MillerIndiana University Melvin and Bren Simon Comprehensive Cancer Center, Indianapolis, IN 46202, USA.
Stephen B BaylinDiakonie-Klinikum Schwäbisch Hall, Germany, Institute for Health Informatics.
Kenneth P NephewMedical Sciences Program, Indiana University School of Medicine-Bloomington, Bloomington, IN 47405, USA.ORCID 0000-0003-2192-1346
Feyruz V RassoolUniversity of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center, Baltimore, MD 21201, USA.

Funding

UNIVERSITY OF MARYLAND GREENEBAUM CANCER CENTERSUPPORT GRANTP30CA134274 · NCI · UNIVERSITY OF MARYLAND BALTIMORE · PI FEYRUZ VIRGILIA RASSOOL · 2008 to 2026
$51.0M
SPORE in Ovarian CancerP50CA228991 · NCI · JOHNS HOPKINS UNIVERSITY · PI Amanda Nickles Fader · 2018 to 2026
$20.5M
Pathology CoreP50CA254897 · NCI · CORIELL INSTITUTE FOR MEDICAL RESEARCH · PI ISSA, JEAN-PIERRE J. · 2021 to 2025
$11.9M
DNA Methyltrasferase Gene Expression in Colon CancerR01ES011858 · NIEHS · JOHNS HOPKINS UNIVERSITY · PI BAYLIN, STEPHEN B., EASWARAN, HARIHARAN · 2002 to 2023
$11.5M
Role of Adaptive Immunity in Etiology of Alzheimer’s Disease andAlzheimer’s Disease-Related DementiasR01AG078814 · NIA · CHILDREN'S HOSP OF PHILADELPHIA · PI Douglas C Wallace · 2022 to 2026
$4.2M
Anti-tumor immunity and intestinal microbiota are modulated by mitochondrial DNAR01CA259635 · NCI · CHILDREN'S HOSP OF PHILADELPHIA · PI Douglas C Wallace · 2022 to 2026
$3.2M
NCI NIH HHS P30 CA134274NCI NIH HHS P50 CA228991NCI NIH HHS P50 CA254897NCI NIH HHS R01 CA259635NIA NIH HHS R01 AG078814NIEHS NIH HHS R01 ES011858
6 · The paper itself

Abstract

DNA methyltransferase and poly(ADP-ribose) polymerase inhibitors (DNMTis, PARPis) induce a stimulator of interferon (IFN) genes (STING)-dependent pathogen mimicry response (PMR) in ovarian (OC) and other cancers. We now show that combining DNMTis and PARPis upregulates expression of a little-studied nucleic-acid sensor, NFX1-type zinc finger-containing 1 protein (ZNFX1). We demonstrate that ZNFX1 is a novel master regulator for PMR induction in mitochondria, serving as a gateway for STING-dependent PMR. In patient OC databases, high ZNFX1 expression levels correlate with advanced stage disease. ZNFX1 expression alone significantly correlates with an increase in overall survival in a phase 3 trial for therapy-resistant OC patients receiving bevacizumab in combination with chemotherapy. In correlative RNA-seq data, inflammasome signaling through ZNFX1 correlates with abnormal vasculogenesis. ZNFX1 controls PMR signaling through the mitochondria and may serve as a biomarker to facilitate offering personalized therapy in OC patients, highlighting the strong translational significance of our findings.

Indexed as

DNA damageinflammasomeinterferonmitochondriaovarian cancerreactive oxygen speciesSTINGtumor suppressorviral mimicryZNFX1

Identifiers

PMID39484607
PMCPMC11526927

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.