Department of Neuropathology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, China.
Tianjin Key Laboratory of Injuries, Variations and Regeneration of the Nervous System, Tianjin, China.
Eur J Clin Invest. 2023 Jun;53(6):e13964. doi: 10.1111/eci.13964. Epub 2023 Feb 13.
Emerging evidence has shown that miR-29 is a promising biomarker and therapeutic target for malignancies. The roles of miR-29a/b/c in glioma pathogenesis remain need further investigation.
The expression levels of miR-29a/b/c and CDC42 were systematically analysed, and prognostic significance was evaluated by Kaplan-Meier survival and Cox regression analyses. The roles of miR-29a/b/c in apoptosis and the underlying mechanisms were explored via an alkaline single-cell gel electrophoresis assay, caspase 3/7 activity assays and Western blotting.
miR-29a/b/c expression decreased progressively with the elevation of the WHO grade in our 147 human glioma specimens, compared with 20 non-tumour control brain tissues, and decreased miR-29a/b/c expression was associated with more aggressive phenotypes. Kaplan-Meier and Cox regression analyses demonstrated that lower miR-29a/b/c expression was correlated with worse prognosis, which was confirmed by analysis of 198 glioma patients from the CGGA cohort. These all indicate that miR-29a/b/c were independent predictors of prognosis in glioma patients. miR-29a/b/c induced apoptosis in GBM cells by silencing CDC42. Further detailed mechanistic investigation revealed that miR-29a/b/c promoted apoptosis in a p53-dependent manner by suppressing the CDC42/PAK/AKT/MDM2 pathway.
miR-29a/b/c are independent predictors of prognosis in glioma patients. They induce glioblastoma cell apoptosis via silencing of CDC42 and suppression of downstream PAK/AKT/MDM2 signalling in a p53-dependent manner.
新出现的证据表明，miR-29 是一种有前途的生物标志物和治疗靶点，可用于多种恶性肿瘤。miR-29a/b/c 在神经胶质瘤发病机制中的作用仍需进一步研究。
系统分析 miR-29a/b/c 和 CDC42 的表达水平，通过 Kaplan-Meier 生存和 Cox 回归分析评估其预后意义。通过碱性单细胞凝胶电泳分析、半胱天冬酶 3/7 活性测定和 Western blot 分析探讨 miR-29a/b/c 在细胞凋亡中的作用及其潜在机制。
在我们的 147 例人胶质瘤标本中，与 20 例非肿瘤对照脑组织相比，miR-29a/b/c 的表达水平随 WHO 分级的升高而逐渐降低，miR-29a/b/c 表达降低与侵袭性表型相关。Kaplan-Meier 和 Cox 回归分析表明，miR-29a/b/c 表达降低与预后不良相关，这在 CGGA 队列的 198 例胶质瘤患者中得到了证实。这些都表明 miR-29a/b/c 是胶质瘤患者独立的预后预测因子。miR-29a/b/c 通过沉默 CDC42 诱导 GBM 细胞凋亡。进一步的详细机制研究表明，miR-29a/b/c 通过抑制 CDC42/PAK/AKT/MDM2 通路，以依赖 p53 的方式促进细胞凋亡。
miR-29a/b/c 是胶质瘤患者独立的预后预测因子。它们通过沉默 CDC42 并抑制下游 PAK/AKT/MDM2 信号通路，以依赖 p53 的方式诱导神经胶质瘤细胞凋亡。
