Evidence map›Paper›PMID 33539420›Full record

ArticlePLoS pathogens2021

CircRNA ARFGEF1 functions as a ceRNA to promote oncogenic KSHV-encoded viral interferon regulatory factor induction of cell invasion and angiogenesis by upregulating glutaredoxin 3.

Shuihong Yao, Xuemei Jia, Fei Wang, Liuxue Sheng, Pengxia Song, Yanhui Cao, Hongjuan Shi, Weifei Fan, Xiangya Ding, Shou-Jiang Gao and 1 more

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in PLoS pathogens, 2021. 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 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
2.7field-weighted citation impact, top 9% 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

26 citing papers in PubMed, 44 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Review
  5. Article
  6. Article
  7. Review
  8. Roles of circRNAs in viral pathogenesis.Frontiers in cellular and infection microbiology · 2025
    Review
  9. Review
  10. Article
  11. Review
  12. Virus-Encoded Circular RNAs: Role and Significance in Viral Infections.International journal of molecular sciences · 2023
    Review
  13. Roles of circRNAs in regulating the tumor microenvironment.Medical oncology (Northwood, London, England) · 2023
    Review
  14. Review
  15. Article
  16. Article
  17. Article
  18. Review
  19. Human Gammaherpesvirus 8 Oncogenes Associated with Kaposi's Sarcoma.International journal of molecular sciences · 2022
    Review
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors at 4 institutions in 2 countries.

Shuihong YaoKey Laboratory of Pathogen Biology of Jiangsu Province, Nanjing Medical University, Nanjing, P. R. China.
Xuemei JiaState Key Laboratory of Reproductive Medicine, Department of Gynecology, Women's Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Hospital, Nanjing Medical University, Nanjing, P. R. China.ORCID 0000-0002-9323-4425
Fei WangDepartment of Microbiology, Nanjing Medical University, Nanjing, P. R. China.
Liuxue ShengDepartment of Microbiology, Nanjing Medical University, Nanjing, P. R. China.
Pengxia SongMedical School, Quzhou College of Technology, Quzhou, P. R. China.
Yanhui CaoMedical School, Quzhou College of Technology, Quzhou, P. R. China.
Hongjuan ShiMedical School, Quzhou College of Technology, Quzhou, P. R. China.
Weifei FanDepartment of Hematology and Oncology, Department of Geriatric Lung Cancer Research Laboratory, Geriatric Hospital of Nanjing Medical University, Nanjing, P. R. China.
Xiangya DingState Key Laboratory of Reproductive Medicine, Department of Gynecology, Women's Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Hospital, Nanjing Medical University, Nanjing, P. R. China.
Shou-Jiang GaoUPMC Hillman Cancer Center, Department of Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.ORCID 0000-0001-6194-1742
Chun LuKey Laboratory of Pathogen Biology of Jiangsu Province, Nanjing Medical University, Nanjing, P. R. China.ORCID 0000-0002-6078-9352
Quzhou College of Technology · CNNanjing Maternity and Child Health Care Hospital · CNNanjing Medical University · 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

Circular RNAs (circRNAs) are novel single-stranded noncoding RNAs that can decoy other RNAs to inhibit their functions. Kaposi's sarcoma (KS), caused by oncogenic Kaposi's sarcoma-associated herpesvirus (KSHV), is a highly angiogenic and invasive vascular tumor of endothelial origin commonly found in AIDS patients. We have recently shown that KSHV-encoded viral interferon regulatory factor 1 (vIRF1) induces cell invasion, angiogenesis and cellular transformation; however, the role of circRNAs is largely unknown in the context of KSHV vIRF1. Herein, transcriptome analysis identified 22 differentially expressed cellular circRNAs regulated by vIRF1 in an endothelial cell line. Among them, circARFGEF1 was the highest upregulated circRNA. Mechanistically, vIRF1 induced circARFGEF1 transcription by binding to transcription factor lymphoid enhancer binding factor 1 (Lef1). Importantly, upregulation of circARFGEF1 was required for vIRF1-induced cell motility, proliferation and in vivo angiogenesis. circARFGEF1 functioned as a competing endogenous RNAs (ceRNAs) by binding to and inducing degradation of miR-125a-3p. Mass spectrometry analysis demonstrated that glutaredoxin 3 (GLRX3) was a direct target of miR-125a-3p. Knockdown of GLRX3 impaired cell motility, proliferation and angiogenesis induced by vIRF1. Taken together, vIRF1 transcriptionally activates circARFGEF1, potentially by binding to Lef1, to promote cell oncogenic phenotypes via inhibiting miR-125a-3p and inducing GLRX3. These findings define a novel mechanism responsible for vIRF1-induced oncogenesis and establish the scientific basis for targeting these molecules for treating KSHV-associated cancers.

Indexed as

Carrier ProteinsCell MovementGuanine Nucleotide Exchange FactorsHerpesvirus 8, HumanHumansHuman Umbilical Vein Endothelial CellsInterferon Regulatory FactorsMicroRNAsNeovascularization, PathologicRNA, CircularSarcoma, KaposiViral ProteinsARFGEF1 protein, humanCarrier ProteinsGLRX3 protein, humanGuanine Nucleotide Exchange FactorsInterferon Regulatory FactorsMicroRNAsMIRN125 microRNA, humanRNA, Circularviral interferon regulatory factorsViral Proteins

Identifiers

PMID33539420
PMCPMC7888650
OpenAlexW3128921519

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.