Correlation between levels of clock protein expression and effects on temozolomide-resistant glioblastoma and tumor progression.

IF 3.4 3区生物学 Q3 CELL BIOLOGY

Human Cell Pub Date : 2025-03-24 DOI:10.1007/s13577-025-01205-y

Keng-Liang Kuo, Shu-Jyuan Chang, Aij-Lie Kwan, Chee-Yin Chai

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引用次数: 0

Abstract

Glioblastoma (GBM) is the most common malignant intracranial neoplasm. Treatment with surgical resection and concurrent chemoradiotherapy may not achieve satisfactory results in life expectancy. Temozolomide (TMZ) chemoresistance is one of the most common reasons for treatment failure, but the role of the circadian cycle and autophagic pathways in this phenomenon is unknown. This study investigated the relationship between the circadian cycle and autophagic pathways in GBM and its TMZ chemoresistance counterpart. The predictive potential of NR1D1 and MGMT was analyzed by using 631 glioma cases derived from the TCGA GBM dataset. Human GBM cell lines (U-87 MG, GBM 8401) and their TMZ chemoresistance counterparts were used for MGMT, circadian proteins (CLOCK, BMAL1, NR1D1), and LC3B analysis. In addition, immunohistochemical staining for NR1D1 was performed in 78 GBM samples, and the results were analyzed with patients' clinicopathological parameters. Results revealed a decrease in NR1D1 expression in GBM cells which could enhance TMZ chemosensitivity. Different expressions of autophagic markers were also noted in GBM cell lines with and without TMZ chemoresistance, indicating a significant role for NR1D1 in TMZ chemoresistance in the GBM cell line. In addition, higher expression of NR1D1 in tumor samples was correlated with poor prognosis and shorter survival. In conclusion, high levels of NR1D1 not only could predict poor prognosis but it could also be used as a chemosensitizer for TMZ in GBM patients.

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胶质母细胞瘤（GBM）是最常见的颅内恶性肿瘤。手术切除和同期放化疗可能无法达到令人满意的预期疗效。替莫唑胺（TMZ）化疗耐药是治疗失败的最常见原因之一，但昼夜节律周期和自噬途径在这一现象中的作用尚不清楚。本研究调查了GBM及其TMZ化疗耐药对应物中昼夜节律周期和自噬途径之间的关系。研究利用 TCGA GBM 数据集中的 631 个胶质瘤病例分析了 NR1D1 和 MGMT 的预测潜力。对人类 GBM 细胞系（U-87 MG、GBM 8401）及其 TMZ 化疗耐药细胞系进行了 MGMT、昼夜节律蛋白（CLOCK、BMAL1、NR1D1）和 LC3B 分析。此外，还对78个GBM样本进行了NR1D1免疫组化染色，并将结果与患者的临床病理参数进行了分析。结果显示，NR1D1在GBM细胞中的表达减少可增强TMZ的化疗敏感性。在有TMZ化疗耐药性和无TMZ化疗耐药性的GBM细胞系中，自噬标记物的表达也有所不同，这表明NR1D1在GBM细胞系的TMZ化疗耐药性中起着重要作用。此外，肿瘤样本中 NR1D1 的高表达与预后不良和生存期缩短相关。总之，高水平的 NR1D1 不仅可以预测预后不良，还可以用作 GBM 患者 TMZ 的化疗增敏剂。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Human Cell CELL BIOLOGY-

CiteScore

5.90

自引率

2.30%

发文量

176

审稿时长

4.5 months

期刊介绍： Human Cell is the official English-language journal of the Japan Human Cell Society. The journal serves as a forum for international research on all aspects of the human cell, encompassing not only cell biology but also pathology, cytology, and oncology, including clinical oncology. Embryonic stem cells derived from animals, regenerative medicine using animal cells, and experimental animal models with implications for human diseases are covered as well. Submissions in any of the following categories will be considered: Research Articles, Cell Lines, Rapid Communications, Reviews, and Letters to the Editor. A brief clinical case report focusing on cellular responses to pathological insults in human studies may also be submitted as a Letter to the Editor in a concise and short format. Not only basic scientists but also gynecologists, oncologists, and other clinical scientists are welcome to submit work expressing new ideas or research using human cells.