Evidence map›Paper›PMID 40639775›Full record

ArticleBiomedical journal2026

Drug repurposing targeting miRNA-mRNA networks to mitigate areca nut-induced head and neck cancer.

Hung-Han Huang, Joseph T Chang, Guo-Rung You, Yi-Chen Li, Yi-Fang Huang, Yu-Chen Huang, Eric Yi-Liang Shen, Yin-Ju Chen, Ching-Chi Chiu, Ann-Joy Cheng

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Article in Biomedical journal, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
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

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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

5 citing papers in PubMed.

  1. Article
  2. The Odyssey of macrophages.Biomedical journal · 2026
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Hung-Han HuangGraduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan; Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
Joseph T ChangDepartment of Radiation Oncology and Proton Therapy Center, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan; School of Medicine, Chang Gung University, Taoyuan, Taiwan.
Guo-Rung YouDepartment of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
Yi-Chen LiClinical Medicine Research Center, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Center of Cell Therapy, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
Yi-Fang HuangDepartment of General Dentistry, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan; Graduate Institute of Dental and Craniofacial Science, College of Medicine, Chang Gung University, Taoyuan, Taiwan; School of Dentistry, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan.
Yu-Chen HuangDepartment of Oral and Maxillofacial Surgery, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan.
Eric Yi-Liang ShenDepartment of Radiation Oncology and Proton Therapy Center, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan.
Yin-Ju ChenGraduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan; Department of Radiation Oncology and Proton Therapy Center, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan; Department of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
Ching-Chi ChiuGraduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan; Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
Ann-Joy ChengGraduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan; Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, Taoyuan, Taiwan; Department of Radiation Oncology and Proton Therapy Center, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan. Electronic address: annjoycheng@gap.cgu.edu.tw.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundAreca nut is a significant risk factor for head and neck cancer (HNC), yet its molecular mechanisms, particularly miRNA-mediated regulation, remain poorly understood. This study investigates the regulatory networks underlying areca nut-induced HNC and explores therapeutic strategies through computational drug repurposing. MATERIALS AND

methodsArecoline was used to assess its effects on invasion, migration, and cisplatin resistance in HNC cells and normal keratinocytes. Differentially expressed miRNAs and mRNAs were identified using high-throughput profiling, followed by integrative network analysis using the TCGA-HNSC dataset and multiMiR. OncoPredict was used for drug repurposing to identify therapeutic agents targeting dysregulated miRNA-mRNA networks.

resultsArecoline exposure promoted invasion and cisplatin resistance, with more pronounced effects in normal keratinocytes, indicating a potential role in early tumorigenesis. Integrative transcriptomic analysis revealed a miRNA-mRNA regulatory network comprising 1971 oncogenes, 604 tumor suppressors, 35 oncogenic miRNA (OncomiRs), and 36 tumor suppressor miRNA (TSmiRs) regulating pathways related to cell motility and stress response. A tumor-suppressive network with miR-212-3p as a central hub and an oncogenic network modulated by miR-410 and miR-1-3p as critical hubs were identified. Drug repurposing analysis identified four potential therapeutic candidates (MK-2206, BYL-719, MG-132, and FGIN-1-27), with MK-2206 emerging as the most promising. MK-2206 effectively reversed arecoline-induced miRNA-mRNA dysregulation, mitigated malignant phenotypes, and selectively targeted HNC cells while sparing normal keratinocytes.

conclusionsThis integrative approach elucidates areca nut-driven carcinogenesis through miRNA-mRNA interactions and highlights MK-2206 as a promising therapeutic strategy for areca nut-associated HNC.

Indexed as

ArecaDrug RepositioningHead and Neck NeoplasmsMicroRNAsRNA, MessengerArecolineCell Line, TumorCell MovementCisplatinGene Expression Regulation, NeoplasticGene Regulatory NetworksHumansKeratinocytesArecolineCisplatinMicroRNAsRNA, MessengerAreca nutDrug repurposingHead and neck cancerMiRNA–mRNA networkMK-2206

Identifiers

PMID40639775
PMCPMC13089172

What OpenQuestion holds

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LicenceCC BY-NC-ND
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Registered trials

None linked

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.