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<p>Glioma, especially high-grade gliomas like glioblastoma, are aggressive and highly treatment-resistant brain tumors with poor prognosis. Despite advances in therapeutic strategies, the mechanisms driving glioma progression remain inadequately understood, with dysregulated apoptosis playing a central role in malignancy. RNA-binding proteins(RBPs) such as the poly(A)-binding protein family, including <i>PABPC5</i>, have gained attention due to their roles in regulating mRNA stability and translation. <i>PABPC5</i>’s role in glioma pathogenesis remains poorly characterized despite its identification as a key regulator of the mitochondria-associated programmed cell death index (mtPCDI) in low-grade glioma (LGG). This study thoroughly investigated the oncogenic functions of <i>PABPC5</i>. TCGA-GBM analysis revealed significant decreasing trend in <i>PABPC5</i> expression with increasing glioma grade(G2 vs. G3:<i>P</i> &lt; 0.05; G2vsG4: <i>P</i> &lt; 0.0001;). However, immunohistochemistry and Western blotting demonstrated that PABPC5 protein levels were elevated in Grade 4 tumors compare to Grades 1–3. Notably, expression levels showed no correlation with overall survival (<i>P</i> = 0.92). Lentiviral infection of <i>PABPC5</i> knockdown in glioblastoma cells (U87/U251) significantly suppressed malignant phenotypes while inducing pro-apoptotic molecular alterations: upregulated BAX and cleaved caspase−3 protein expression, enhanced ROS production, and reduced Bcl−2 and caspase−3 levels. In vivo validation showed that <i>PABPC5</i> knocdown substantially inhibited subcutaneous tumor growth and increased apoptosis (TUNEL:3.164-fold increase,<i>P</i> &lt; 0.001). Consistent with in vitro findings, immunofluorescence(IF)analysis of tumor tissues confirmed altered Bcl−2/cleaved-caspase−3 expression patterns and mitochondrial ultrastructural changes. This work establishes PABPC5 as a novel biomarker for glioma pathological grading and reveals its functional role in apoptosis regulation. These findings provide a mechanistic foundation for developing therapeutic strategies targeting apoptosis-resistant glioma.</p>

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Mechanistic insights into PABPC5-mediated regulation of apoptosis in glioma pathophysiology

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年1月30日

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  • A Mujite,
  • Yitong Zheng,
  • Wen Liu,
  • Yabin Li,
  • Xiaohu Ma,
  • Batulu Hu,
  • Tengfei Liu,
  • Wude Su,
  • Hu Qin,
  • Yongxin Wang

摘要

Glioma, especially high-grade gliomas like glioblastoma, are aggressive and highly treatment-resistant brain tumors with poor prognosis. Despite advances in therapeutic strategies, the mechanisms driving glioma progression remain inadequately understood, with dysregulated apoptosis playing a central role in malignancy. RNA-binding proteins(RBPs) such as the poly(A)-binding protein family, including PABPC5, have gained attention due to their roles in regulating mRNA stability and translation. PABPC5’s role in glioma pathogenesis remains poorly characterized despite its identification as a key regulator of the mitochondria-associated programmed cell death index (mtPCDI) in low-grade glioma (LGG). This study thoroughly investigated the oncogenic functions of PABPC5. TCGA-GBM analysis revealed significant decreasing trend in PABPC5 expression with increasing glioma grade(G2 vs. G3:P < 0.05; G2vsG4: P < 0.0001;). However, immunohistochemistry and Western blotting demonstrated that PABPC5 protein levels were elevated in Grade 4 tumors compare to Grades 1–3. Notably, expression levels showed no correlation with overall survival (P = 0.92). Lentiviral infection of PABPC5 knockdown in glioblastoma cells (U87/U251) significantly suppressed malignant phenotypes while inducing pro-apoptotic molecular alterations: upregulated BAX and cleaved caspase−3 protein expression, enhanced ROS production, and reduced Bcl−2 and caspase−3 levels. In vivo validation showed that PABPC5 knocdown substantially inhibited subcutaneous tumor growth and increased apoptosis (TUNEL:3.164-fold increase,P < 0.001). Consistent with in vitro findings, immunofluorescence(IF)analysis of tumor tissues confirmed altered Bcl−2/cleaved-caspase−3 expression patterns and mitochondrial ultrastructural changes. This work establishes PABPC5 as a novel biomarker for glioma pathological grading and reveals its functional role in apoptosis regulation. These findings provide a mechanistic foundation for developing therapeutic strategies targeting apoptosis-resistant glioma.