Zheng Wenying, Shang Yanyan, DU Kai, Luo Ailing, Pei Lijun, Li Meiqi, Zhang Guoping, Deng Min
Guangzhou Institute of Cancer Research, The Affiliated Cancer Hospital, Guangzhou Medical University, Guangzhou, 510095, China.
Medical Oncology, Yuebei People Hospital, Shaoguan, 512026, China.
Oncol Res. 2025 Apr 18;33(5):1121-1133. doi: 10.32604/or.2025.060958. eCollection 2025.
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.
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 and 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.
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 and suppressed hepatocarcinoma xenograft growth and infiltration . 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 () gene and promoting oncogene expression. Notably, the dysregulation of MAPT splicing coincided with increased PTBP1 expression in HCC.
PTBP1-guided AS of the gene enhances tumorigenicity in HCC through activation of the MAPK/ERK pathways.
剪接因子的改变会导致异常可变剪接（AS），进而促进肿瘤进展。剪接因子多嘧啶序列结合蛋白1（PTBP1）已被证明可通过调节致癌变体来促进癌症进展。然而，其在肝细胞癌（HCC）中的具体作用和潜在机制仍有待阐明。
评估PTBP1在肝癌组织和细胞系中的表达。随后，用设计用于PTBP1过表达或下调的载体转染细胞。使用MTS试验、集落形成试验、Transwell试验、异种移植形成、尾静脉注射和原位模型评估PTBP1的生物学功能。进行转录组分析以阐明潜在的分子机制。
我们的研究结果表明，PTBP1在肝癌细胞系和组织中表达升高。此外，其表达与总生存率和无病生存率以及肿瘤分级和分期呈正相关。PTBP1敲低降低了肝癌细胞的增殖、迁移和侵袭，并抑制了肝癌异种移植的生长和浸润。RNA测序（RNA-Seq）分析确定了与PTBP1相关的AS事件。PTBP1通过调节微管相关蛋白tau（）基因的AS并促进癌基因表达，在功能上增强了细胞增殖、侵袭和迁移。值得注意的是，MAPT剪接失调与肝癌中PTBP1表达增加相一致。
PTBP1引导的基因AS通过激活MAPK/ERK途径增强肝癌的致瘤性。
