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染色质重塑因子 MORC2 在癌症中的作用的新见解。

Novel Insights into the Role of Chromatin Remodeler MORC2 in Cancer.

机构信息

Biology Division, Indian Institute of Science Education and Research (IISER) Tirupati, Mangalam, Tirupati 517 507, India.

Department of Biochemistry, School of Life Sciences, University of Hyderabad, Hyderabad 500 046, India.

出版信息

Biomolecules. 2023 Oct 15;13(10):1527. doi: 10.3390/biom13101527.

Abstract

A newly discovered chromatin remodeler, MORC2, is a Microrchidia (MORC) family member. MORC2 acts as a chromatin remodeler by binding to the DNA and changing chromatin conformation using its ATPase domain. MORC2 is highly expressed in a variety of human cancers. It controls diverse signaling pathways essential for cancer development through its target genes and interacting partners. MORC2 promotes cancer cells' growth, invasion, and migration by regulating the expression of genes involved in these processes. MORC2 is localized primarily in the nucleus and is also found in the cytoplasm. In the cytoplasm, MORC2 interacts with adenosine triphosphate (ATP)-citrate lyase (ACLY) to promote lipogenesis and cholesterogenesis in cancer. In the nucleus, MORC2 interacts with the transcription factor c-Myc to control the transcription of genes involved in glucose metabolism to drive cancer cell migration and invasion. Furthermore, MORC2 recruits on to the promoters of tumor suppressor genes to repress their transcription and expression to promote oncogenesis. In addition to its crucial function in oncogenesis, it plays a vital role in DNA repair. Overall, this review concisely summarizes the current knowledge about MORC2-regulated molecular pathways involved in cancer.

摘要

新发现的染色质重塑因子 MORC2 是 Microrchidia (MORC) 家族的一员。MORC2 通过结合 DNA 并利用其 ATP 酶结构域改变染色质构象来充当染色质重塑因子。MORC2 在多种人类癌症中高度表达。它通过其靶基因和相互作用伙伴控制对癌症发展至关重要的各种信号通路。MORC2 通过调节参与这些过程的基因的表达来促进癌细胞的生长、侵袭和迁移。MORC2 主要定位于细胞核内,也存在于细胞质中。在细胞质中,MORC2 与三磷酸腺苷(ATP)-柠檬酸裂解酶(ACLY)相互作用,以促进癌症中的脂肪生成和胆固醇生成。在细胞核内,MORC2 与转录因子 c-Myc 相互作用,以控制参与葡萄糖代谢的基因的转录,从而驱动癌细胞的迁移和侵袭。此外,MORC2 将自身募集到肿瘤抑制基因的启动子上,抑制它们的转录和表达,以促进致癌作用。除了在致癌作用中的关键功能外,它在 DNA 修复中也起着至关重要的作用。总之,这篇综述简明扼要地总结了目前关于 MORC2 调节的涉及癌症的分子途径的知识。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b56b/10605154/dec41df24037/biomolecules-13-01527-g001.jpg

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