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<p><i>Pre-B-cell leukemia homeobox 1</i> (<i>PBX1</i>) is a transcription factor involved in diverse cellular processes, but its role in colorectal cancer (CRC) remains incompletely understood. In this study, we show that <i>PBX1</i> is downregulated in CRC tissues and cell lines. Functional experiments revealed that <i>PBX1</i> overexpression inhibits proliferation, migration, and invasion, but paradoxically suppresses apoptosis, suggesting a dual regulatory role. Transcriptome and CUT&amp;Tag profiling identified <i>BCL2L1</i> as a direct transcriptional target of PBX1. PBX1 binds the <i>BCL2L1</i> promoter and enhances Bcl-xL expression, contributing to apoptotic resistance. <i>BCL2L1</i> knockdown reversed the anti-apoptotic effects of <i>PBX1</i> and restored apoptosis levels. Upon 5-fluorouracil (5-FU) treatment, <i>PBX1</i> overexpression reduced cell viability, while concurrent <i>BCL2L1</i> knockdown significantly enhanced drug sensitivity. In vivo, xenograft experiments demonstrated that <i>PBX1</i> overexpression suppressed tumor growth, which was further augmented by <i>BCL2L1</i> knockdown. These results support the dual role of <i>PBX1</i> in simultaneously inhibiting tumor growth while promoting cell survival through the <i>BCL2L1</i>–Bcl-xL axis. This regulatory interaction may influence tumor persistence and therapeutic response in CRC.</p>

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Targeting the PBX1–BCL2L1 axis as a therapeutic strategy in colorectal cancer

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年5月5日

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  • Hao Lin,
  • Ting Su,
  • Ying Liu,
  • Ruilan Deng,
  • Jie Li,
  • Xuanhao Lin,
  • Qiaoling Ke,
  • Yijing Luo,
  • Lele Meng,
  • Bin Liang,
  • Xuhong Song,
  • Dongyang Huang,
  • Lingzhu Xie

摘要

Pre-B-cell leukemia homeobox 1 (PBX1) is a transcription factor involved in diverse cellular processes, but its role in colorectal cancer (CRC) remains incompletely understood. In this study, we show that PBX1 is downregulated in CRC tissues and cell lines. Functional experiments revealed that PBX1 overexpression inhibits proliferation, migration, and invasion, but paradoxically suppresses apoptosis, suggesting a dual regulatory role. Transcriptome and CUT&Tag profiling identified BCL2L1 as a direct transcriptional target of PBX1. PBX1 binds the BCL2L1 promoter and enhances Bcl-xL expression, contributing to apoptotic resistance. BCL2L1 knockdown reversed the anti-apoptotic effects of PBX1 and restored apoptosis levels. Upon 5-fluorouracil (5-FU) treatment, PBX1 overexpression reduced cell viability, while concurrent BCL2L1 knockdown significantly enhanced drug sensitivity. In vivo, xenograft experiments demonstrated that PBX1 overexpression suppressed tumor growth, which was further augmented by BCL2L1 knockdown. These results support the dual role of PBX1 in simultaneously inhibiting tumor growth while promoting cell survival through the BCL2L1–Bcl-xL axis. This regulatory interaction may influence tumor persistence and therapeutic response in CRC.