Background: Hepatocellular carcinoma is a fatal malignancy that lacking specific therapies. Homeobox B4 (HOXB4) was negatively correlated with poor prognosis in cancers, but its role in hepatocellular carcinoma has not been elucidated.
Results: We confirmed that HOXB4 was downregulated in hepatocellular carcinoma tissues and lower HOXB4 expression associated with poor prognosis. Gain- and loss-of function experiments were performed to understand the functional consequences. We revealed that HOXB4 overexpression inhibited proliferation and metastasis of hepatocellular carcinoma cells, accompanied with the decrease in epithelial-mesenchymal transition and increase in cell apoptosis. Database analysis showed that HOXB4 was positively correlated with the immune infiltration. PD-L1 expression was decreased in HOXB4 overexpressed hepatocellular carcinoma cells. HOXB4 overexpression was confirmed to inhibit the progression of hepatocellular carcinoma and promote T cell infiltration in vivo. N6-methyladenosine (m6A) modification was implicated in the tumorigenesis. RNA-seq analysis showed that HOXB4 overexpression modulated METTL7B expression. With the performance of dual-luciferase reporter, ChIP, and DNA pulldown assays, we revealed that HOXB4 binding to METTL7B promoter and inhibited its mRNA expression. The increased aggressiveness of hepatocellular carcinoma cells and the enhanced immune escape, triggered by HOXB4 knockdown, were inhibited via METTL7B downregulation. Methylated RNA immunoprecipitation assay displayed that METTL7B controlled the mRNA decay of TKT in m6A methylation. METTL7B overexpression increase the expression of TKT, ultimately promoting hepatocellular carcinoma progression and immune evasion.
Conclusions: HOXB4 mediated the malignant phenotypes and modulated the immune evasion via METTL7B/TKT axis. The HOXB4/METTL7B cascade and its downstream changes might be novel targets for blocking hepatocellular carcinoma progression.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11884015 | PMC |
| http://dx.doi.org/10.1186/s13062-025-00620-3 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Transplantation of Patients with Hepatocellular Carcinoma Through Increased Utilization of Machine Perfusion Technology.
Transplant Direct
April 2025
Division of Surgical Transplantation, Department of Surgery, University of Texas Southwestern Medical Center, Dallas, TX.
Background: With the intent to mitigate waitlist disparities, the median model for end-stage liver disease (MELD) at transplant minus 3 policy nevertheless decreased access to liver transplant for patients with hepatocellular carcinoma (HCC). However, the adoption of machine perfusion (MP) technologies has shown promise in improving deceased donor graft yield and utilization. To understand current use for patients with HCC, we examined liver transplant patterns with MP and the characteristics of patients with HCC receiving an MP liver.
View Article and Find Full Text PDFClinical spectrum and uncommon features of McCune-Albright syndrome in children: a cohort study from a National Referral Center.
Front Endocrinol (Lausanne)
March 2025
Hospices Civils de Lyon, Hôpital Femme Mère Enfant, Service d'Endocrinologie Pédiatrique et Pédiatrie Générale, Bron, France.
Introduction: McCune-Albright syndrome (MAS) is a rare disease caused by somatic gain-of-function variants in the gene that lead to constitutive activation of the G protein alpha subunit (Gsα). Pathologic consequences can involve several tissues. Fibrous dysplasia (FD), café-au-lait skin macules and hyperfunctioning endocrinopathies are classic manifestations.
View Article and Find Full Text PDFProanthocyanidin B2 alleviates LPS-induced RAW264.7 cellular inflammation and oxidative stress via PI3K/Akt/NFkB pathway.
Cytotechnology
April 2025
The Affiliated Stomatological Hospital, Jiangxi Medical College, Nanchang University, NO.688, Honggu North Road, Honggu Tan District, Nanchang City, 330038 Jiangxi Province China.
Periodontitis is a multifactorial chronic inflammatory infectious disease associated with systemic diseases. Proanthocyanidin B2 (PB2), a polyphenol, has been investigated to exhibit antioxidant, anti-inflammatory and anti-cancer pharmacological properties. PB2 has shown good efficacy in treating hepatocellular carcinoma, type 2 diabetes mellitus, and ulcerative colitis.
View Article and Find Full Text PDFImpact of viral eradication by direct-acting antivirals on clinical outcomes after curative treatment for hepatitis C virus-associated hepatocellular carcinoma.
Therap Adv Gastroenterol
March 2025
Department of Gastroenterology, Graduate School of Biomedical and Health Science, Hiroshima University, Hiroshima, Japan.
Background: It is not clear that antiviral therapy for hepatitis C virus (HCV) after recovery from curative treatment for hepatocellular carcinoma (HCC) has an effect on suppressing recurrence or improving survival rates.
Objectives: We analyzed the impact of eradication by interferon (IFN)-free direct-acting antiviral (DAA) therapy on clinical outcomes of patients with HCV-associated HCC who underwent curative treatment.
Design: This was a retrospective study.
Knowledge structure and dynamic evolution of nanomedicine in liver cancer research: a scientometric analysis and visualization.
Front Pharmacol
February 2025
Department of Colorectal and Anal Surgery, General Surgery Center, First Hospital of Jilin University, Changchun, China.
Background: Nanomedicine has received much attention for its potential applications in the diagnosis and treatment of liver cancer. However, no bibliometric evaluation has been conducted to present an assessment of scientific progress in the field. The aim of this study is to comprehensively catalog the cooperation and influence of journals, countries, institutions, and authors in the field of nanomedicine in liver cancer from the perspective of bibliometrics, evaluate the clustering evolution of knowledge structure, and uncover hot topics and emerging themes.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!