Jiaxin Huang, Jiaqi Tan, Nanfeng Meng, Junrong Wang, Peng Han, Hang Wang
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The transcription factor HOXB7 significantly enhances the expression of PIGT through the Wnt/β-catenin signaling pathway, thereby promoting the proliferation and deterioration of HCC.
Background: Glycosylphosphatidylinositol-anchored proteins (GPI-APs) contribute to cancer progression, with their glycolipid modification mediated by glycosylphosphatidylinositol transamidase (GPIT). Phosphatidylinositol glycan anchor biosynthesis class T (PIGT), a key GPIT subunit, influences GPI-APs biosynthesis and tumor biology. This study investigates PIGT expression in hepatocellular carcinoma (HCC) and its regulatory mechanisms.
Methods: HCC genome sequencing and The Cancer Genome Atlas (TCGA) database were analyzed to compare PIGT expression between tumor and adjacent normal tissues. PIGT knockdown and overexpression cell lines examined its influence on HCC cell proliferation, migration, and invasion. Gene Set Enrichment Analysis (GSEA) identified downstream pathways, and Japan Australia Singapore Profiling Array Repository (JASPAR) predicted upstream transcriptional regulators, which were validated by in vivo tumor models.
Results: PIGT was upregulated in HCC, enhancing tumor cell aggressiveness. GSEA implicated oncogenic pathways, and JASPAR identified homeobox B7 (HOXB7) as key transcriptional regulator. Animal models validated HOXB7-induced PIGT upregulation and its role in HCC progression.
Conclusions: PIGT promotes HCC malignancy via the Wnt/β-catenin pathway, with HOXB7 as its upstream regulator.
期刊介绍：
Expert Review of Anticancer Therapy (ISSN 1473-7140) provides expert appraisal and commentary on the major trends in cancer care and highlights the performance of new therapeutic and diagnostic approaches.
Coverage includes tumor management, novel medicines, anticancer agents and chemotherapy, biological therapy, cancer vaccines, therapeutic indications, biomarkers and diagnostics, and treatment guidelines. All articles are subject to rigorous peer-review, and the journal makes an essential contribution to decision-making in cancer care.
Comprehensive coverage in each review is complemented by the unique Expert Review format and includes the following sections:
Expert Opinion - a personal view of the data presented in the article, a discussion on the developments that are likely to be important in the future, and the avenues of research likely to become exciting as further studies yield more detailed results
Article Highlights – an executive summary of the author’s most critical points.
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