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利用表观遗传学进行乳腺癌治疗:DNA 甲基化、组蛋白修饰和 microRNA 的作用。

Harnessing Epigenetics for Breast Cancer Therapy: The Role of DNA Methylation, Histone Modifications, and MicroRNA.

机构信息

Centre for Modern Interdisciplinary Technologies, Nicolaus Copernicus University, 87-100 Torun, Poland.

Faculty of Biological and Veterinary Sciences, Nicolaus Copernicus University, 87-100 Torun, Poland.

出版信息

Int J Mol Sci. 2023 Apr 13;24(8):7235. doi: 10.3390/ijms24087235.

Abstract

Breast cancer exhibits various epigenetic abnormalities that regulate gene expression and contribute to tumor characteristics. Epigenetic alterations play a significant role in cancer development and progression, and epigenetic-targeting drugs such as DNA methyltransferase inhibitors, histone-modifying enzymes, and mRNA regulators (such as miRNA mimics and antagomiRs) can reverse these alterations. Therefore, these epigenetic-targeting drugs are promising candidates for cancer treatment. However, there is currently no effective epi-drug monotherapy for breast cancer. Combining epigenetic drugs with conventional therapies has yielded positive outcomes and may be a promising strategy for breast cancer therapy. DNA methyltransferase inhibitors, such as azacitidine, and histone deacetylase inhibitors, such as vorinostat, have been used in combination with chemotherapy to treat breast cancer. miRNA regulators, such as miRNA mimics and antagomiRs, can alter the expression of specific genes involved in cancer development. miRNA mimics, such as miR-34, have been used to inhibit tumor growth, while antagomiRs, such as anti-miR-10b, have been used to inhibit metastasis. The development of epi-drugs that target specific epigenetic changes may lead to more effective monotherapy options in the future.

摘要

乳腺癌表现出各种表观遗传异常,这些异常调节基因表达,促进肿瘤特征的形成。表观遗传改变在癌症的发生和发展中起着重要作用,表观遗传靶向药物,如 DNA 甲基转移酶抑制剂、组蛋白修饰酶和 mRNA 调节剂(如 miRNA 模拟物和反义寡核苷酸),可以逆转这些改变。因此,这些表观遗传靶向药物是癌症治疗的有前途的候选药物。然而,目前尚无针对乳腺癌的有效单药表观遗传治疗药物。将表观遗传药物与传统疗法联合使用已取得积极成果,可能是乳腺癌治疗的一种有前途的策略。DNA 甲基转移酶抑制剂,如阿扎胞苷,和组蛋白去乙酰化酶抑制剂,如伏立诺他,已与化疗联合用于治疗乳腺癌。miRNA 调节剂,如 miRNA 模拟物和反义寡核苷酸,可以改变参与癌症发展的特定基因的表达。miRNA 模拟物,如 miR-34,已被用于抑制肿瘤生长,而反义寡核苷酸,如 anti-miR-10b,已被用于抑制转移。针对特定表观遗传变化的表观遗传药物的开发可能会导致未来更有效的单药治疗选择。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/321e/10138995/98c1d038ada5/ijms-24-07235-g001.jpg

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