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Article Open Access

Integrated microRNA‑mRNA network analysis of invasive and immune‑inflammatory pathways in sebaceous carcinoma of the eyelid with pagetoid spread

  • Authors:
    • Tatsuya Yunoki
    • Tetsushi Hirano
    • Yukihiro Furusawa
    • Yoshiaki Tabuchi
    • Atsushi Hayashi
  • View Affiliations / Copyright

    Affiliations: Department of Ophthalmology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama 930‑0194, Japan, Division of Molecular Genetics Research, Life Science Research Center, University of Toyama, Toyama 930‑0194, Japan, Department of Liberal Arts and Sciences, Toyama Prefectural University, Toyama 939‑0398, Japan
    Copyright: © Yunoki et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 37
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    Published online on: March 30, 2026
       https://doi.org/10.3892/mco.2026.2946
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Abstract

Pagetoid spread is a poor prognostic factor in sebaceous carcinoma (SGC) of the eyelid; however, its underlying molecular mechanisms remain unclear. The present study aimed to investigate the expression profiles of microRNAs (miRNAs/miRs) and mRNAs in SGC of the eyelid with pagetoid spread, compared with cases without pagetoid spread, and to explore potential miRNA‑mRNA regulatory networks. Total RNA was extracted from three patients with SGC of the eyelid with pagetoid spread (pagetoid group), three patients without pagetoid spread (non‑pagetoid group), and three patients with normal tarsal plate tissue obtained during free tarsal plate reconstruction (control group). Small RNA sequencing was performed using a next‑generation sequencer to identify differentially expressed miRNAs among the groups, and bioinformatics analyses of mRNA expression profiles were conducted to determine associated biological functions and construct miRNA‑mRNA interaction networks. In the pagetoid group, upregulated mRNAs and downregulated miRNAs were associated with enhanced invasion, migration and immune‑inflammatory responses. Three miRNAs, miR‑1275, miR‑1976 and miR‑330‑5p, were commonly involved in these functional networks. Conversely, downregulated mRNAs and upregulated miRNAs were associated with impaired lipid metabolism, including miR‑760‑3p, miR‑1266‑5p, miR‑3918, miR‑1269a and miR‑198. These findings suggest that SGC of the eyelid with pagetoid spread demonstrates increased invasive and migratory capacity, reduced lipid metabolic function and enhanced immune‑inflammatory responses, which may contribute to its aggressive biological behavior. Introduction
View Figures

Figure 1

Venn diagrams of differentially
expressed mRNAs and microRNAs in SGC classified by pagetoid spread
status. (A) mRNAs with ≥2-fold upregulation compared with controls.
(B) microRNAs with ≥1.5-fold downregulation compared with controls.
The diagrams illustrate unique and shared differentially expressed
genes or microRNAs between pagetoid-positive and pagetoid-negative
SGC groups. SGC, sebaceous gland carcinoma.

Figure 2

Venn diagrams of differentially
expressed transcripts of mRNAs and microRNAs in SGC classified by
pagetoid spread status. (A) mRNAs with ≥2-fold downregulation
compared with controls. (B) microRNAs with ≥1.5-fold upregulation
compared with controls. The diagrams depict unique and shared
differentially expressed transcripts between pagetoid-positive and
pagetoid-negative SGC groups. SGC, sebaceous gland carcinoma.

Figure 3

Molecular network of cell
migration-related genes regulated by three downregulated microRNAs
and eleven upregulated mRNAs. The network illustrates the
interactions between three downregulated microRNAs and eleven
upregulated mRNAs involved in the biological function ‘migration of
cells’. Predicted or validated microRNA-mRNA interactions are
shown, indicating potential regulatory relationships contributing
to enhanced cell motility.

Figure 4

Molecular network related to
lymphocyte activation involving three downregulated microRNAs and
eleven upregulated mRNAs. The figure depicts a regulatory network
associated with the biological function ‘activation of
lymphocytes’. The network includes three downregulated microRNAs
and eleven upregulated mRNAs, illustrating predicted or validated
miRNA-mRNA interactions that may contribute to enhanced lymphocyte
activity.

Figure 5

Molecular network related to fatty
acid metabolism involving five upregulated microRNAs and eight
downregulated mRNAs. The figure illustrates a molecular network
associated with the biological function ‘fatty acid metabolism’.
The network includes five upregulated microRNAs and eight
downregulated mRNAs, depicting predicted or experimentally
supported miRNA-mRNA interactions that may play a role in the
regulation of lipid metabolic processes.
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Copy and paste a formatted citation
Spandidos Publications style
Yunoki T, Hirano T, Furusawa Y, Tabuchi Y and Hayashi A: Integrated microRNA‑mRNA network analysis of invasive and immune‑inflammatory pathways in sebaceous carcinoma of the eyelid with pagetoid spread. Mol Clin Oncol 24: 37, 2026.
APA
Yunoki, T., Hirano, T., Furusawa, Y., Tabuchi, Y., & Hayashi, A. (2026). Integrated microRNA‑mRNA network analysis of invasive and immune‑inflammatory pathways in sebaceous carcinoma of the eyelid with pagetoid spread. Molecular and Clinical Oncology, 24, 37. https://doi.org/10.3892/mco.2026.2946
MLA
Yunoki, T., Hirano, T., Furusawa, Y., Tabuchi, Y., Hayashi, A."Integrated microRNA‑mRNA network analysis of invasive and immune‑inflammatory pathways in sebaceous carcinoma of the eyelid with pagetoid spread". Molecular and Clinical Oncology 24.5 (2026): 37.
Chicago
Yunoki, T., Hirano, T., Furusawa, Y., Tabuchi, Y., Hayashi, A."Integrated microRNA‑mRNA network analysis of invasive and immune‑inflammatory pathways in sebaceous carcinoma of the eyelid with pagetoid spread". Molecular and Clinical Oncology 24, no. 5 (2026): 37. https://doi.org/10.3892/mco.2026.2946
Copy and paste a formatted citation
x
Spandidos Publications style
Yunoki T, Hirano T, Furusawa Y, Tabuchi Y and Hayashi A: Integrated microRNA‑mRNA network analysis of invasive and immune‑inflammatory pathways in sebaceous carcinoma of the eyelid with pagetoid spread. Mol Clin Oncol 24: 37, 2026.
APA
Yunoki, T., Hirano, T., Furusawa, Y., Tabuchi, Y., & Hayashi, A. (2026). Integrated microRNA‑mRNA network analysis of invasive and immune‑inflammatory pathways in sebaceous carcinoma of the eyelid with pagetoid spread. Molecular and Clinical Oncology, 24, 37. https://doi.org/10.3892/mco.2026.2946
MLA
Yunoki, T., Hirano, T., Furusawa, Y., Tabuchi, Y., Hayashi, A."Integrated microRNA‑mRNA network analysis of invasive and immune‑inflammatory pathways in sebaceous carcinoma of the eyelid with pagetoid spread". Molecular and Clinical Oncology 24.5 (2026): 37.
Chicago
Yunoki, T., Hirano, T., Furusawa, Y., Tabuchi, Y., Hayashi, A."Integrated microRNA‑mRNA network analysis of invasive and immune‑inflammatory pathways in sebaceous carcinoma of the eyelid with pagetoid spread". Molecular and Clinical Oncology 24, no. 5 (2026): 37. https://doi.org/10.3892/mco.2026.2946
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