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表观遗传药物和表观遗传微小RNA:超越当前癌症治疗方法

Epi-Drugs and Epi-miRs: Moving Beyond Current Cancer Therapies.

作者信息

Salarinia Reza, Sahebkar Amirhossein, Peyvandi Mostafa, Mirzaei Hamid Reza, Jaafari Mahmoud Reza, Riahi Maryam Matbou, Ebrahimnejad Hamed, Nahand Javid Sadri, Hadjati Jamshid, Asrami Mobina Ostadi, Fadaei Sara, Salehi Rasoul, Mirzaei Hamed

机构信息

Department of Medical Genetics, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.

Department of Medical Biotechnology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

出版信息

Curr Cancer Drug Targets. 2016;16(9):773-788. doi: 10.2174/1568009616666151207110143.

Abstract

Epigenetic modifications determine phenotypic characteristics in a reversible, stable and genotype-independent manner. Epigenetic modifications mainly encompass CpG island methylation and histone modifications, both being important in the pathogenesis of malignancies. The reversibility of epigenetic phenomenon provides a suitable therapeutic option that is reactivation of epigenetically silenced tumor-suppressor genes. Inhibition of DNA methyltransferase, histone deacetylase and Aurora B kinase, individually or collectively, could feasibly prevent or reverse the impact of epigenetic silencing. MicroRNAs [miRNAs] are an important layer of epigenetic controlling of gene expression, and serve as diagnostic and prognostic biomarkers as well as treatment targets for several types of cancer. miRNAs are involved inepigenetically silencing or activation of genes, tumor suppressor genes and oncogenes, and their modulation opens new horizons for designing novel cancer therapeutic agents.

摘要

表观遗传修饰以一种可逆、稳定且不依赖基因型的方式决定表型特征。表观遗传修饰主要包括CpG岛甲基化和组蛋白修饰,二者在恶性肿瘤的发病机制中均起重要作用。表观遗传现象的可逆性提供了一种合适的治疗选择,即重新激活表观遗传沉默的肿瘤抑制基因。单独或联合抑制DNA甲基转移酶、组蛋白脱乙酰酶和极光激酶B,可能有效预防或逆转表观遗传沉默的影响。微小RNA(miRNA)是基因表达表观遗传调控的重要层面,可作为多种癌症的诊断和预后生物标志物以及治疗靶点。miRNA参与基因、肿瘤抑制基因和癌基因的表观遗传沉默或激活,对其进行调控为设计新型癌症治疗药物开辟了新途径。

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