2. Academic Validation
  3. TUBB4A Inhibits Glioma Development by Regulating ROS-PINK1/Parkin-Mitophagy Pathway

TUBB4A Inhibits Glioma Development by Regulating ROS-PINK1/Parkin-Mitophagy Pathway

  • Mol Neurobiol. 2024 Sep 4. doi: 10.1007/s12035-024-04459-z.
Xueru Xi 1,  Suqin Chen 1,  Xiaoli Zhao 1,  Zimu Zhou 2,  Shanjie Zhu 1,  Xurui Ren 1,  Xiaomei Wang 1,  Jing Wu 3,  Shuai Mu 4,  Xianwen Li 5,  Enfang Shan 6,  Yan Cui 7
Affiliations

Affiliations

  • 1 School of Nursing, Nanjing Medical University, Nanjing, China.
  • 2 The Cancer Research Institute, Hengyang Medical College, University of South China, Hengyang, Hunan, China.
  • 3 Department of Anesthesiology, The First Medical Center of Chinese, PLA General Hospital, Beijing, China.
  • 4 Department of Oncology, Senior Department of Oncology, The First Medical Center of Chinese People's Liberation Army (PLA) General Hospital, Beijing, China.
  • 5 School of Nursing, Nanjing Medical University, Nanjing, China. xwli0201@njmu.edu.cn.
  • 6 School of Nursing, Nanjing Medical University, Nanjing, China. shanenfang@njmu.edu.cn.
  • 7 School of Nursing, Nanjing Medical University, Nanjing, China. cyan@njmu.edu.cn.
PMID: 39230869 DOI: 10.1007/s12035-024-04459-z
Abstract

Glioma is a refractory malignant tumor with a powerful capacity for invasiveness and a poor prognosis. This study aims to investigate the role and mechanism of tubulin beta class IVA (TUBB4A) in glioma progression. The differential expression of TUBB4A in humans was obtained from databases and analyzed. Glioma cells U251-MG and U87-MG were intervened by pcDNA3.1(+) and TUBB4A overexpression plasmid. MTT, CCK8, LDH, wound healing, transwell, and western blotting were used to explore whether TUBB4A participates in the development of glioma. Reactive Oxygen Species (ROS) were detected by the DCFH-DA probe. Mitochondrial membrane potential (MMP) was examined by JC-1. It was found that TUBB4A expression level correlated with tumor grade, IDH1 status, 1p/19q status, and poor survival in glioma patients. In addition, TUBB4A overexpression inhibited the proliferation, migration, and invasion of U251-MG and U87-MG, while increasing the degree of Apoptosis. Notably, TUBB4A overexpression promotes ROS generation and MMP depolarization, and induces Mitophagy through the PINK1/Parkin pathway. Interestingly, mitochondria-targeted ROS scavenger reversed the effect of TUBB4A overexpression on PINK1/Parkin expression and Mitophagy, whereas Mitophagy inhibitor did not affect ROS production. And the effect of TUBB4A overexpression on Mitophagy and glioma progression was consistent with that of PINK1/Parkin agonist. In conclusion, TUBB4A is a molecular marker for predicting the prognosis of glioma patients and an effective target for inhibiting glioma progression by regulating ROS-PINK1/Parkin-mitophagy pathway.

Keywords

Glioma; Mitophagy; PINK1/Parkin; ROS; TUBB4A.

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