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Review Open Access

Role of COUP‑TFII in cardiovascular diseases and colorectal cancer: Insights into the molecular mechanisms and clinical relevance (Review)

  • Authors:
    • Tae-Ho Park
    • Sang-Heum Han
    • Jun-Gi Cho
    • Su-Jeong Park
    • Jin-Yeong Han
    • Joo-In Park
  • View Affiliations / Copyright

    Affiliations: Department of Internal Medicine, Dong‑A University College of Medicine, Busan 49201, Republic of Korea, Department of Biochemistry, Dong‑A University College of Medicine, Busan 49201, Republic of Korea, Department of Laboratory Medicine, Dong‑A University College of Medicine, Busan 49201, Republic of Korea
    Copyright: © Park et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 266
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    Published online on: July 22, 2025
       https://doi.org/10.3892/mmr.2025.13631
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Abstract

Chicken ovalbumin upstream promoter‑transcription factor II (COUP‑TFII), also known as nuclear receptor subfamily 2 group F member 2, is an orphan nuclear receptor that controls various biological processes, including development, angiogenesis, metabolism and tissue homeostasis. Structurally, COUP‑TFII comprises a DNA‑binding domain and a ligand‑binding domain, facilitating its interaction with various signaling pathways, and thereby exerting diverse biological effects. Alterations of the expression or transcriptional activity of COUP‑TFII are associated with various diseases, including cardiovascular diseases (CVDs) and different types of cancer such as colorectal cancer (CRC). In the context of CVDs, COUP‑TFII serves a key role in the development and function of the vascular system. Dysregulation of COUP‑TFII leads to aberrant angiogenesis and vascular remodeling, contributing to the pathogenesis of various CVDs. In CRC, COUP‑TFII acts as either a tumor suppressor or a tumor promoter, depending on the cellular context. The present review explores the structure and regulatory mechanisms of COUP‑TFII, its functions and molecular mechanisms in CVDs and CRC, and its emerging role in linking these diseases, offering insights into potential treatments and future research directions.
View Figures

Figure 1

Structure and transcriptional
regulatory mechanism of COUP-TFII. (A) Schematic structure of the
human COUP-TFII protein. The numbers represent the positions of
amino acids. (B) Transcriptional regulatory mechanism of COUP-TFII.
COUP-TFII binds to the 5′-AGGTCA-3′ motif or palindromic sequences
with various spacings (DR site), either directly (homodimer) or
indirectly, through heterodimer formation with other proteins (such
as RXR) to regulate downstream target gene expression. COUP-TFII
can also bind to Sp1 sites via interaction with Sp1 to
cooperatively activate gene expression. COUP-TFII, chicken
ovalbumin upstream promoter-transcription factor II; RXR, retinoid
X receptor; Sp1, specificity protein 1; TSS1, transcription start
site 1; DBD, DNA-binding domain; LBD, ligand-binding domain; AF,
activation function; DR, direct repeat.

Figure 2

Schematic illustration of the
molecular mechanisms by which COUP-TFII functions as a common
regulator in both CVDs and CRC. Although CVDs and CRC are distinct
disease entities, they share common pathophysiological features. In
particular, chronic inflammation, oxidative stress, angiogenesis
and metabolic dysregulation by COUP-TFII may serve roles in the
pathogenesis of both conditions. COUP-TFII, chicken ovalbumin
upstream promoter-transcription factor II; EC, endothelial cell;
EndMT, endothelial-to-mesenchymal transition; ETC, electron
transport chain; Ang-1, angiopoietin-1; EMT,
epithelial-to-mesenchymal transition; CVD, cardiovascular disease;
CRC, colorectal cancer; PAH, pulmonary arterial hypertension.
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Copy and paste a formatted citation
Spandidos Publications style
Park T, Han S, Cho J, Park S, Han J and Park J: Role of COUP‑TFII in cardiovascular diseases and colorectal cancer: Insights into the molecular mechanisms and clinical relevance (Review). Mol Med Rep 32: 266, 2025.
APA
Park, T., Han, S., Cho, J., Park, S., Han, J., & Park, J. (2025). Role of COUP‑TFII in cardiovascular diseases and colorectal cancer: Insights into the molecular mechanisms and clinical relevance (Review). Molecular Medicine Reports, 32, 266. https://doi.org/10.3892/mmr.2025.13631
MLA
Park, T., Han, S., Cho, J., Park, S., Han, J., Park, J."Role of COUP‑TFII in cardiovascular diseases and colorectal cancer: Insights into the molecular mechanisms and clinical relevance (Review)". Molecular Medicine Reports 32.4 (2025): 266.
Chicago
Park, T., Han, S., Cho, J., Park, S., Han, J., Park, J."Role of COUP‑TFII in cardiovascular diseases and colorectal cancer: Insights into the molecular mechanisms and clinical relevance (Review)". Molecular Medicine Reports 32, no. 4 (2025): 266. https://doi.org/10.3892/mmr.2025.13631
Copy and paste a formatted citation
x
Spandidos Publications style
Park T, Han S, Cho J, Park S, Han J and Park J: Role of COUP‑TFII in cardiovascular diseases and colorectal cancer: Insights into the molecular mechanisms and clinical relevance (Review). Mol Med Rep 32: 266, 2025.
APA
Park, T., Han, S., Cho, J., Park, S., Han, J., & Park, J. (2025). Role of COUP‑TFII in cardiovascular diseases and colorectal cancer: Insights into the molecular mechanisms and clinical relevance (Review). Molecular Medicine Reports, 32, 266. https://doi.org/10.3892/mmr.2025.13631
MLA
Park, T., Han, S., Cho, J., Park, S., Han, J., Park, J."Role of COUP‑TFII in cardiovascular diseases and colorectal cancer: Insights into the molecular mechanisms and clinical relevance (Review)". Molecular Medicine Reports 32.4 (2025): 266.
Chicago
Park, T., Han, S., Cho, J., Park, S., Han, J., Park, J."Role of COUP‑TFII in cardiovascular diseases and colorectal cancer: Insights into the molecular mechanisms and clinical relevance (Review)". Molecular Medicine Reports 32, no. 4 (2025): 266. https://doi.org/10.3892/mmr.2025.13631
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