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Article

High Mobility Group Box 1 Is Potential Target Therapy for Inhibiting Metastasis and Enhancing Drug Sensitivity of Hepatocellular Carcinoma

by
Arunya Jiraviriyakul
1,2,
Chatchai Nensat
1,3,
Samitanan Promchai
4,
Yanisa Chaiaun
5,
Yanisa Hoiraya
5,
Nutnicha Yamnak
5,
Suphakit Khutanthong
6,
Nun Singpan
6 and
Worawat Songjang
1,2,*
1
Integrative Biomedical Research Unit (IBRU), Faculty of Allied Health Sciences, Naresuan University, Phitsanulok 65000, Thailand
2
Department of Medical Technology, Faculty of Allied Health Sciences, Naresuan University, Phitsanulok 65000, Thailand
3
Department of Cardio-Thoracic Technology, Faculty of Allied Health Sciences, Naresuan University, Phitsanulok 65000, Thailand
4
Biomedical Sciences Program, Faculty of Allied Health Sciences, Naresuan University, Phitsanulok 65000, Thailand
5
Medical Technology Program, Faculty of Allied Health Sciences, Naresuan University, Phitsanulok 65000, Thailand
6
Department of Pathology, Faculty of Medicine, Naresuan University, Phitsanulok 65000, Thailand
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2025, 26(8), 3491; https://doi.org/10.3390/ijms26083491
Submission received: 28 January 2025 / Revised: 6 April 2025 / Accepted: 7 April 2025 / Published: 8 April 2025
(This article belongs to the Special Issue Advancing Cancer Research: Molecular Insights, Diagnostic Innovations and Therapeutic Targets)
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Abstract

Hepatocellular carcinoma (HCC) is a lethal malignancy associated with drug resistance, resulting in a poor prognosis. High mobility group box 1 (HMGB1) is a chromatin-binding protein that regulates HCC progression. The overexpression of HMGB1 has been found to promote tumorigenesis and drug resistance. In this study, we aimed to investigate the role of HMGB1 expression in tumorigenesis and metastasis and its impact on sorafenib and oxaliplatin resistance. Tissue samples from patients with HCC (n = 48) were subjected to immunohistochemistry. The expression of HMGB1 was correlated with clinical pathology parameters. Moreover, the HCC cell line HuH-7 was used to study the regulatory effect of HMGB1 on cell proliferation, cell adhesion, migration, and invasion by using the siRNA (small interfering RNA) silencing method. Furthermore, drug challenges were performed to determine the effect of HMGB1 on the sensitivity to chemotherapeutic drugs (sorafenib and oxaliplatin). HMGB1 was significantly overexpressed in tumor tissues, highlighted by the expression increment in patients with M1 advanced metastasis tumors with immunoreactivity scores 2.61 and 6.50 for adjacent and tumor tissues, respectively (p-values = 0.0035). The involved mechanisms were then described through the suppression of HCC cell adhesion, migration, and invasion by HMGB1 silencing. Notably, the inhibition of HMGB1 expression promoted sorafenib/oxaliplatin sensitivity in the HCC cell line by increasing the cell toxicity by about 13–18%. Our study demonstrated that HMGB1 shows potential as a promising biomarker and a target for HCC treatment that is involved in tumorigenesis, metastasis, and chemo-drug resistance.
Keywords: high mobility group box 1 (HMGB1); hepatocellular carcinoma (HCC); metastasis; sorafenib; oxaliplatin high mobility group box 1 (HMGB1); hepatocellular carcinoma (HCC); metastasis; sorafenib; oxaliplatin

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MDPI and ACS Style

Jiraviriyakul, A.; Nensat, C.; Promchai, S.; Chaiaun, Y.; Hoiraya, Y.; Yamnak, N.; Khutanthong, S.; Singpan, N.; Songjang, W. High Mobility Group Box 1 Is Potential Target Therapy for Inhibiting Metastasis and Enhancing Drug Sensitivity of Hepatocellular Carcinoma. Int. J. Mol. Sci. 2025, 26, 3491. https://doi.org/10.3390/ijms26083491

AMA Style

Jiraviriyakul A, Nensat C, Promchai S, Chaiaun Y, Hoiraya Y, Yamnak N, Khutanthong S, Singpan N, Songjang W. High Mobility Group Box 1 Is Potential Target Therapy for Inhibiting Metastasis and Enhancing Drug Sensitivity of Hepatocellular Carcinoma. International Journal of Molecular Sciences. 2025; 26(8):3491. https://doi.org/10.3390/ijms26083491

Chicago/Turabian Style

Jiraviriyakul, Arunya, Chatchai Nensat, Samitanan Promchai, Yanisa Chaiaun, Yanisa Hoiraya, Nutnicha Yamnak, Suphakit Khutanthong, Nun Singpan, and Worawat Songjang. 2025. "High Mobility Group Box 1 Is Potential Target Therapy for Inhibiting Metastasis and Enhancing Drug Sensitivity of Hepatocellular Carcinoma" International Journal of Molecular Sciences 26, no. 8: 3491. https://doi.org/10.3390/ijms26083491

APA Style

Jiraviriyakul, A., Nensat, C., Promchai, S., Chaiaun, Y., Hoiraya, Y., Yamnak, N., Khutanthong, S., Singpan, N., & Songjang, W. (2025). High Mobility Group Box 1 Is Potential Target Therapy for Inhibiting Metastasis and Enhancing Drug Sensitivity of Hepatocellular Carcinoma. International Journal of Molecular Sciences, 26(8), 3491. https://doi.org/10.3390/ijms26083491

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