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液-液相分离在人类癌症中作用的研究进展

[Research Progress in the Role of Liquid-Liquid Phase Separation in Human Cancer].

作者信息

Tao Ruolin, Zhang Shuijun, Guo Wenzhi, Yan Zhiping

机构信息

( 450000) Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450000, China.

( 450000) Henan Key Laboratory for Digestive Organ Transplantation, Zhengzhou 450000, China.

出版信息

Sichuan Da Xue Xue Bao Yi Xue Ban. 2024 Jan 20;55(1):24-30. doi: 10.12182/20240160503.

Abstract

Liquid-liquid phase separation (LLPS) is a reversible process, during which biological macromolecules, including proteins and nucleic acids, condense into liquid membraneless organelles under the influence of weak multivalent interactions. Currently, fluorescence recovery after photobleaching is the primary method used to detect the phase separation of biological macromolecules. Recent studies have revealed the link between abnormal LLPS and the pathogenesis and development of various human cancers. Through phase separation or abnormal phase separation, tumor-related biological macromolecules, such as mRNA, long noncoding RNAs (lncRNAs), and tumor-related proteins, can affect transcriptional translation and DNA damage repair, regulate the autophagy and ferroptosis functions of cells, and thus regulate the development of various tumors. In this review, we summarized the latest research findings on the mechanism of LLPS in the pathogenesis and progression of tumors and elaborated on the promotion or inhibition of autophagy, tumor immunity, DNA damage repair, and cell ferroptosis after abnormal phase separation of biomolecules, including mRNA, lncRNA, and proteins, which subsequently affects the pathogenesis and progression of tumors. According to published findings, many biological macromolecules can regulate transcriptional translation, expression, post-transcriptional modification, cell signal transduction, and other biological processes through phase separation. Therefore, further expansion of the research field of phase separation and in-depth investigation of its molecular mechanisms and regulatory processes hold extensive research potential.

摘要

液-液相分离(LLPS)是一个可逆过程,在此过程中,包括蛋白质和核酸在内的生物大分子在弱多价相互作用的影响下凝聚成无膜细胞器。目前,光漂白后荧光恢复是用于检测生物大分子相分离的主要方法。最近的研究揭示了异常液-液相分离与各种人类癌症的发病机制和发展之间的联系。通过相分离或异常相分离,与肿瘤相关的生物大分子,如信使核糖核酸(mRNA)、长链非编码核糖核酸(lncRNA)和与肿瘤相关的蛋白质,可以影响转录翻译和DNA损伤修复,调节细胞的自噬和铁死亡功能,从而调控各种肿瘤的发展。在这篇综述中,我们总结了液-液相分离在肿瘤发病机制和进展中的最新研究发现,并阐述了生物分子(包括mRNA、lncRNA和蛋白质)异常相分离后对自噬、肿瘤免疫、DNA损伤修复和细胞铁死亡的促进或抑制作用,这些作用随后影响肿瘤的发病机制和进展。根据已发表的研究结果,许多生物大分子可以通过相分离调节转录翻译、表达、转录后修饰、细胞信号转导等生物学过程。因此,进一步拓展相分离研究领域,深入探究其分子机制和调控过程具有广泛的研究潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dea9/10839487/1253c2ed55c7/scdxxbyxb-55-1-24-1.jpg

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