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Cited by 41Cancer, Hypoxia, and MetabolismCancer Immunotherapy and BiomarkersHepatocellular Carcinoma Treatment and Prognosis

The DOI matches its Crossref record; 2 of the 2 references it cites were found in a registry or an index.

Cancer cell-associated cytoplasmic B7–H4 is induced by hypoxia through hypoxia-inducible factor-1α and promotes cancer cell proliferation

Jeon, You-Kyoung, Park, Sae-Gwang, Choi, Il-Whan, Lee, Soo-Woong, Lee, Sang Min, Choi, Inhak·2015·Biochemical and Biophysical Research Communications
DOI 10.1016/j.bbrc.2015.02.098
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Abstract

Aberrant B7-H4 expression in cancer tissues serves as a novel prognostic biomarker for poor survival in patients with cancer. However, the factor(s) that induce cancer cell-associated B7-H4 remain to be fully elucidated. We herein demonstrate that hypoxia upregulates B7-H4 transcription in primary CD138(+) multiple myeloma cells and cancer cell lines. In support of this finding, analysis of the Multiple Myeloma Genomics Portal (MMGP) data set revealed a positive correlation between the mRNA expression levels of B7-H4 and the endogenous hypoxia marker carbonic anhydrogenase 9. Hypoxia-induced B7-H4 expression was detected in the cytoplasm, but not in cancer cell membranes. Chromatin immunoprecipitation analysis demonstrated binding of hypoxia-inducible factor-1α (HIF-1α) to proximal hypoxia-response element (HRE) sites within the B7-H4 promoter. Knockdown of HIF-1α and pharmacological inhibition of HIF-1α diminished B7-H4 expression. Furthermore, knockdown of cytoplasmic B7-H4 in MCF-7 decreased the S-phase cell population under hypoxia. Finally, MMGP analysis revealed a positive correlation between the transcript levels of B7-H4 and proliferation-related genes including MKI67, CCNA1, and Myc in several patients with multiple myeloma. Our results provide insight into the mechanisms underlying B7-H4 upregulation and its role in cancer cell proliferation in a hypoxic tumor microenvironment.

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Research works printed but not linked: 23

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Cited by

Sorted by citations

  • HIF inhibitor 32-134D eradicates murine hepatocellular carcinoma in combination with anti-PD1 therapy

    Salman, S., Meyers, D. J., Wicks, E. E., Lee, S. N., Datan, E., Thomas, A. M., Anders, N. M., Hwang, Y., Lyu, Y., Yang, Y., et al. (2022) · Journal of Clinical Investigation · doi:10.1172/jci156774 · Cited by 111

    “B7H4 and TIM3 mRNA, which are encoded by the Vtcn1 and Havcr2 genes, respectively, and like PDL1, encode immune checkpoint receptors that are HIF regulated (51, 52) and associated with patient mortality in HCC (53), showed hypoxia-induced expression in vehicle-treated but not in 32-134D–treated cells (P < 0.”
    BackgroundSelf-citation

Metadata

Authors
Jeon, Y.-K., Park, S.-G., Choi, I.-W., Lee, S.-W., Lee, S. M., & Choi, I.
Affiliations
Inje University (KR)
Corresponding author
Choi, Inhak
ORCID
Venue
Biochemical and Biophysical Research Communications
Publisher
Elsevier BV
Published
2015-04
Volume
459
Issue
2
Pages
277-283
ISSN
0006-291X (ISSN-L)
DOI
10.1016/j.bbrc.2015.02.098
OpenAlex
W1991090387
Cited by
41
References
2
Citations by year
2026: 3 · 2025: 3 · 2024: 3 · 2023: 3 · 2022: 11 · 2021: 2 · 2020: 3 · 2019: 2 · 2018: 3 · 2017: 6 · 2016: 1 · 2015: 1
FWCI
1.21
Type
journal article
Language
en
Open access
closed
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Biochemical and Biophysical Research Communications (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National R&D Program for Cancer Control
  • Ministry of Health
  • Welfare and Family Affairs, Republic of Korea (0920040)
  • National Research Foundation of Korea (NRF)
  • MSIP (R13-2007-023-00000-0)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
  • Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
  • Health Sciences › Medicine › Hepatology › Hepatocellular Carcinoma Treatment and Prognosis
Keywords
B7-H4, hypoxia, hypoxia-inducible factor-1α, multiple myeloma, carbonic anhydrase IX, hypoxia response element, tumor cell proliferation, tumor microenvironment, prognostic factors, MCF-7 cells
MeSH terms
Cytoplasm, Humans, Multiple Myeloma, Promoter Regions, Genetic, Recombinant Proteins, Cell Hypoxia, Gene Expression Regulation, Neoplastic, Cell Line, Tumor, Chromatin Immunoprecipitation, Cell Proliferation, Hypoxia-Inducible Factor 1, alpha Subunit, Gene Knockdown Techniques, Tumor Microenvironment, V-Set Domain-Containing T-Cell Activation Inhibitor 1, MCF-7 Cells

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