Evidence map›Paper›PMID 32776977›Full record

ArticlePLoS pathogens2020

Sperm associated antigen 9 promotes oncogenic KSHV-encoded interferon regulatory factor-induced cellular transformation and angiogenesis by activating the JNK/VEGFA pathway.

Wan Li, Fei Wang, Jiale Shi, Qi Feng, Yuheng Chen, Xiaoyu Qi, Cong Wang, Hongmei Lu, Zhongmou Lu, Xuemei Jia and 3 more

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in PLoS pathogens, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
1.3field-weighted citation impact, top 18% of its field
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

15 citing papers in PubMed, 16 citations in OpenAlex.

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  7. Cancer/Testis Antigens as Targets for RNA-Based Anticancer Therapy.International journal of molecular sciences · 2023
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  15. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors at 4 institutions in 2 countries.

Wan LiDepartment of Microbiology, Nanjing Medical University, Nanjing, People's Republic of China.
Fei WangDepartment of Microbiology, Nanjing Medical University, Nanjing, People's Republic of China.
Jiale ShiDepartment of Microbiology, Nanjing Medical University, Nanjing, People's Republic of China.
Qi FengDepartment of Microbiology, Nanjing Medical University, Nanjing, People's Republic of China.
Yuheng ChenDepartment of Microbiology, Nanjing Medical University, Nanjing, People's Republic of China.
Xiaoyu QiDepartment of Microbiology, Nanjing Medical University, Nanjing, People's Republic of China.
Cong WangDepartment of Pathology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, People's Republic of China.
Hongmei LuDepartment of Obstetrics, the First Affiliated Hospital of Nanjing Medical University, Nanjing, People's Republic of China.
Zhongmou LuDepartment of Microbiology, Nanjing Medical University, Nanjing, People's Republic of China.
Xuemei JiaDepartment of Gynecology, Women's Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Hospital, Nanjing Medical University, Nanjing, People's Republic of China.
Qin YanDepartment of Microbiology, Nanjing Medical University, Nanjing, People's Republic of China.
Shou-Jiang GaoUPMC Hillman Cancer Center, Department of Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
Chun LuDepartment of Microbiology, Nanjing Medical University, Nanjing, People's Republic of China.ORCID 0000-0002-6078-9352
Nanjing Medical University · CNNanjing Maternity and Child Health Care Hospital · CNJiangsu Province Hospital · CNUPMC Hillman Cancer Center · US

Funding

HISTONE MODIFIERS IN ORAL KSHV INFECTION AND MALIGNANCIESR01DE025465 · NIDCR · UNIVERSITY OF SOUTHERN CALIFORNIA · PI GAO, SHOU-JIANG · 2015 to 2019
$2.0M
Targeting KSHV malignancies and persistent infectionR01CA197153 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI GAO, SHOU-JIANG · 2015 to 2019
$1.9M
KSHV microRNAs in tumor invasion and angiogenesisR01CA213275 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI GAO, SHOU-JIANG · 2017 to 2021
$959k
NCI NIH HHS R01 CA197153NCI NIH HHS R01 CA213275NIDCR NIH HHS R01 DE025465
6 · The paper itself

Abstract

Kaposi's sarcoma (KS), caused by Kaposi's sarcoma-associated herpesvirus (KSHV), is a highly angioproliferative disseminated tumor of endothelial cells commonly found in AIDS patients. We have recently shown that KSHV-encoded viral interferon regulatory factor 1 (vIRF1) mediates KSHV-induced cell motility (PLoS Pathog. 2019 Jan 30;15(1):e1007578). However, the role of vIRF1 in KSHV-induced cellular transformation and angiogenesis remains unknown. Here, we show that vIRF1 promotes angiogenesis by upregulating sperm associated antigen 9 (SPAG9) using two in vivo angiogenesis models including the chick chorioallantoic membrane assay (CAM) and the matrigel plug angiogenesis assay in mice. Mechanistically, vIRF1 interacts with transcription factor Lef1 to promote SPAG9 transcription. vIRF1-induced SPAG9 promotes the interaction of mitogen-activated protein kinase kinase 4 (MKK4) with JNK1/2 to increase their phosphorylation, resulting in enhanced VEGFA expression, angiogenesis, cell proliferation and migration. Finally, genetic deletion of ORF-K9 from KSHV genome abolishes KSHV-induced cellular transformation and impairs angiogenesis. Our results reveal that vIRF1 transcriptionally activates SPAG9 expression to promote angiogenesis and tumorigenesis via activating JNK/VEGFA signaling. These novel findings define the mechanism of KSHV induction of the SPAG9/JNK/VEGFA pathway and establish the scientific basis for targeting this pathway for treating KSHV-associated cancers.

Indexed as

Adaptor Proteins, Signal TransducingAnimalsCell Transformation, NeoplasticHerpesvirus 8, HumanHost-Pathogen InteractionsHumansInterferon Regulatory FactorsMaleMiceMitogen-Activated Protein Kinase 8Mitogen-Activated Protein Kinase 9Neovascularization, PathologicSarcoma, KaposiVascular Endothelial Growth Factor AViral ProteinsAdaptor Proteins, Signal TransducingInterferon Regulatory FactorsMitogen-Activated Protein Kinase 8Mitogen-Activated Protein Kinase 9SPAG9 protein, humanVascular Endothelial Growth Factor AVEGFA protein, humanviral interferon regulatory factorsViral Proteins

Identifiers

PMID32776977
PMCPMC7446834
OpenAlexW3048537925

What OpenQuestion holds

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LicenceCC BY
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.