@Article{or.2025.060958,
AUTHOR = {WENYING ZHENG, YANYAN SHANG, KAI DU, AILING LUO, LIJUN PEI, MEIQI LI, GUOPING ZHANG, MIN DENG},
TITLE = {Splicing factor PTBP1 promotes hepatocarcinogenesis via oncogenic splice-switching of MAPT},
JOURNAL = {Oncology Research},
VOLUME = {33},
YEAR = {2025},
NUMBER = {5},
PAGES = {1121--1133},
URL = {http://www.techscience.com/or/v33n5/60624},
ISSN = {1555-3906},
ABSTRACT = { <b>Background:</b> Alterations in splicing factors contribute to aberrant alternative splicing (AS), which subsequently promotes tumor progression. The splicing factor polypyrimidine tract binding protein 1 (PTBP1) has been shown to facilitate cancer progression by modulating oncogenic variants. However, its specific role and underlying mechanisms in hepatocellular carcinoma (HCC) remain to be elucidated. <b>Methods:</b> PTBP1 expression was evaluated in HCC tissues and cell lines. Subsequently, cells were transfected with vectors designed for PTBP1 overexpression or downregulation. The biological function of PTBP1 was assessed <i>in vitro</i> and <i>in vivo</i> using MTS assays, colony formation assays, transwell assays, xenograft formation, tail vein injection, and orthotopic models. Transcriptome analysis was conducted to elucidate the underlying molecular mechanisms. <b>Results:</b> Our findings demonstrated that PTBP1 exhibited elevated expression in HCC cell lines and tissues. Furthermore, its expression positively correlated with overall and disease-free survival rates, as well as tumor grade and stage. PTBP1 knockdown reduced HCC cell proliferation, migration, and invasion <i>in vitro</i> and suppressed hepatocarcinoma xenograft growth and infiltration <i>in vivo</i>. RNA sequencing (RNA-Seq) analysis identified the AS events associated with PTBP1. PTBP1 functionally enhanced cell proliferation, invasion, and migration by modulating the AS of the microtubule-associated protein tau (<i>MAPT</i>) gene and promoting oncogene expression. Notably, the dysregulation of MAPT splicing coincided with increased PTBP1 expression in HCC. <b>Conclusions:</b> PTBP1-guided AS of the <i>MAPT</i> gene enhances tumorigenicity in HCC through activation of the MAPK/ERK pathways.},
DOI = {10.32604/or.2025.060958}
}