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B-MYB原癌基因启动子区域中的I-基序形成。

I-motif formation in the promoter region of the B-MYB proto-oncogene.

作者信息

Alves André, Miranda André, Zanin Irene, Richter Sara N, Mergny Jean-Louis, Cruz Carla

机构信息

CICS-UBI - Health Sciences Research Centre, University of Beira Interior, Covilhã, Portugal.

CICS-UBI - Health Sciences Research Centre, University of Beira Interior, Covilhã, Portugal; RISE-Health, Departamento de Química, Faculdade de Ciências, Universidade da Beira Interior, Rua Marquês d'Ávila e Bolama, 6201-001 Covilhã, Portugal.

出版信息

Int J Biol Macromol. 2025 Mar;296:139582. doi: 10.1016/j.ijbiomac.2025.139582. Epub 2025 Jan 9.

Abstract

Understanding the mechanisms of carcinogenesis is essential to combat cancer. The search for alternative targets for anticancer therapy has gained interest, particularly when focused on upstream pathways. This strategy is particularly relevant when the encoded target proteins are known - or believed - to be "undruggable", as has been reported for the B-MYB oncogene. This gene, which regulates survival and cell cycle regulation, is overexpressed in cancer and correlates with an unfavorable prognosis. In this study, we focused on the identification of the i-motif (iM) structures in the promoter region of B-MYB as a possible anticancer target, with a complete biophysical characterization and in cell formation assessment using iM-CUT&Tag. Additionally, the interaction of the iM structures with a library of small molecules was investigated.

摘要

了解致癌机制对于对抗癌症至关重要。寻找抗癌治疗的替代靶点已引起关注,特别是当聚焦于上游通路时。当编码的靶蛋白已知或被认为是“不可成药的”时,这种策略尤为重要,如B-MYB癌基因的情况。该基因调节细胞存活和细胞周期调控,在癌症中过度表达并与不良预后相关。在本研究中,我们专注于鉴定B-MYB启动子区域中的i-基序(iM)结构作为可能的抗癌靶点,并使用iM-CUT&Tag进行完整的生物物理表征和细胞内形成评估。此外,还研究了iM结构与小分子文库的相互作用。

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