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脑肿瘤的表观遗传学及其在放射治疗中的调控:综述。

The epigenetics of brain tumors and its modulation during radiation: A review.

机构信息

Radiation Biology Lab, 206, ASK-II, School of Chemical and Biotechnology, SASTRA Deemed University, Thanjavur, Tamil Nadu 613401, India.

Department of Bioinformatics, School of Chemical and Biotechnology, SASTRA Deemed University, Thanjavur, Tamil Nadu 613401, India.

出版信息

Life Sci. 2020 Sep 1;256:117974. doi: 10.1016/j.lfs.2020.117974. Epub 2020 Jun 15.

Abstract

The brain tumor is the abnormal growth of heterogeneous cells around the central nervous system and spinal cord. Most clinically prominent brain tumors affecting both adult and pediatric are glioblastoma, medulloblastoma, and ependymoma and they are classified according to their origin of tissue. Chemotherapy, radiotherapy, and surgery are important treatments available to date. However, these treatments fail due to multiple reasons, including chemoresistance and radiation resistance of cancer cells. Thus, there is a need of new therapeutic designs to target cell signaling and molecular events which are responsible for this resistance. Recently epigenetic changes received increased attention because it helps in understanding chromatin-mediated disease mechanism. The epigenetic modification alters chromatin structure that affects the docking site of many drugs which cause chemo-resistance of cancer therapy. This review centers the mechanism of how epigenetic changes affect the transcription repression and activation of various genes including Polycomb gene, V-Myc avian myelocytomatosis viral oncogene (MYCN). This review also put forth the pathway of radiation-induced reactive oxygen species generation and its role in epigenetic changes in the cellular level and its impact on tissue physiology. Additionally, there is a strong relationship between the behavior of an individual and environment-induced epigenetic regulation of gene expression. The review also discusses Transcriptome heterogeneity and role of tumor microenvironment in glioblastoma. Overall, this review emphasis important and novel epigenetic targets that could be of therapeutic benefit, which helps in overcoming the unsolved chromatin alteration in brain cancer.

摘要

脑肿瘤是中枢神经系统和脊髓周围异质细胞的异常生长。最常见的影响成人和儿童的临床脑肿瘤是胶质母细胞瘤、髓母细胞瘤和室管膜瘤,它们根据其组织来源进行分类。化疗、放疗和手术是目前重要的治疗方法。然而,由于多种原因,包括癌细胞的化疗耐药性和放疗耐药性,这些治疗方法都失败了。因此,需要新的治疗设计来针对细胞信号和分子事件,这些事件是导致耐药性的原因。最近,表观遗传变化受到了越来越多的关注,因为它有助于理解染色质介导的疾病机制。表观遗传修饰改变了染色质结构,影响了许多药物的结合位点,从而导致癌症治疗的化疗耐药性。这篇综述集中讨论了表观遗传变化如何影响转录抑制和各种基因(包括多梳基因、V-Myc 禽髓细胞瘤病毒致癌基因(MYCN))的激活的机制。这篇综述还提出了辐射诱导活性氧生成的途径及其在细胞水平上对表观遗传变化的作用及其对组织生理学的影响。此外,个体行为与环境诱导的基因表达表观遗传调控之间存在很强的关系。这篇综述还讨论了转录组异质性和肿瘤微环境在胶质母细胞瘤中的作用。总的来说,这篇综述强调了重要的和新的表观遗传靶点,这可能具有治疗益处,有助于克服脑癌中未解决的染色质改变。

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