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Cited by 179MicroRNA in disease regulationCytokine Signaling Pathways and Interactionsinterferon and immune responses

IFN Induces miR-21 through a Signal Transducer and Activator of Transcription 3–Dependent Pathway as a Suppressive Negative Feedback on IFN-Induced Apoptosis

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Yang, Chuan He, Yue, Junming, Fan, Meiyun, Pfeffer, Lawrence M.·2010·Cancer Research
DOI 10.1158/0008-5472.can-10-2579PMC PMC3014825

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Abstract

The microRNA miR-21 is overexpressed in many human cancers, wherein accumulating evidence indicates that it functions as an oncogene. Here, we report that the cytokine IFN rapidly induces miR-21 expression in human and mouse cells. Signal transducer and activator of transcription 3 (STAT3) was implicated in this pathway based on the lack of IFN effect on miR-21 expression in prostate cancer cells with a deletion in the STAT3 gene. STAT3 ablation abrogated IFN induction of miR-21, confirming the important role of STAT3 in regulating miR-21. Chromatin immunoprecipitation analysis showed that STAT3 directly bound the miR-21 promoter in response to IFN. Experiments in mouse embryo fibroblasts with a genetic deletion of the p65 NF-κB subunit showed that IFN-induced miR-21 expression was also dependent on NF-κB. STAT3 silencing blocked both IFN-induced p65 binding to the miR-21 promoter and p65 nuclear translocation. Thus, IFN-induced miR-21 expression is coregulated by STAT3 and NF-κB at the level of the miR-21 promoter. Several cell death regulators were identified as downstream targets of miR-21, including PTEN and Akt. Functional experiments in prostate cancer cells directly showed that miR-21 plays a critical role in suppressing IFN-induced apoptosis. Our results identify miR-21 as a novel IFN target gene that functions as a key feedback regulator of IFN-induced apoptosis.

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  • Modulating miR-21 expression in in vivo and in vitro studies shows clear and important phenotype changes.

    “Modulating its expression in in vivo and in vitro studies show clear and important phenotype changes.”

    From miR-21: a non‐specific biomarker of all maladies (2021) · cites this paper as [16]

    The Results section, “miR-21 expression suppresses IFN-induced apoptosis” (page unavailable), reports clear changes in apoptosis after miR-21 overexpression or knockdown in cultured cancer cells. Our copy does not report an in vivo experiment showing a phenotype change, so it supports only the in vitro part of the claim. (LLM, conf=0.87)

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Research works printed but not linked: 1

  1. [5]Yang CH Shi W Basu L Direct association of STAT3 with the IFNAR1 signal transducing chain of the type I IFN receptor J Biol Chem 1996 271 8057 61 8626489

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Authors
Yang, C. H., Yue, J., Fan, M., & Pfeffer, L. M.
Affiliations
University of Tennessee Health Science Center (US)
Corresponding author
Pfeffer, Lawrence M.
ORCID
Venue
Cancer Research
Publisher
American Association for Cancer Research (AACR)
Published
2010-10-13
Volume
70
Issue
20
Pages
8108-8116
ISSN
  • 0008-5472 (ISSN-L)
  • 1538-7445
DOI
10.1158/0008-5472.can-10-2579
PMC
PMC3014825
OpenAlex
W2072751712
Cited by
179
References
31
Citations by year
2026: 2 · 2025: 5 · 2024: 8 · 2023: 9 · 2022: 4 · 2021: 8 · 2020: 9 · 2019: 7 · 2018: 9 · 2017: 11 · 2016: 17 · 2015: 24 · 2014: 16 · 2013: 15 · 2012: 20
FWCI
5.04
Type
journal article
Language
en
Open access
Locations
  • Cancer Research (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • Biogen
  • IC Design Education Center
  • U.S. Public Health Service (RHL095957)
  • National Heart, Lung, and Blood Institute (R21HL095957)
  • National Cancer Institute (R01CA133322, CA133322, R01CA140346)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
  • Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
  • Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
Keywords
miR-21, interferon, STAT3, NF-κB, NF-κB p65, negative feedback regulation, apoptosis, PTEN, Akt, prostate cancer, microRNA regulation, oncogenes
MeSH terms
Animals, Feedback, Fibroblasts, Humans, Interferons, Male, Prostatic Neoplasms, Signal Transduction, Apoptosis, DNA Primers, DNA, Complementary, Mice, Knockout, Gene Silencing, MicroRNAs, STAT3 Transcription Factor, Mice, Transcription Factor RelA

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