Mechanism of Paraspeckles in Regulating DNA Damage Response and Its Role in Carcinogenesis and Cancer Development

ZHANG Yuxin¹, CHEN Wen¹, LIANG Qihui¹, DING Shengyong², WU Haicui³*

（¹First Clinical College of Shandong University of Traditional Chinese Medicine, Jinan 250014, China; ²Pharmacy Department of Shandong University of Traditional Chinese Medicine Affiliated Hospital, Jinan 250014, China; ³Reproductive and Genetic Department of Shandong University of Traditional Chinese Medicine Affiliated Hospital, Jinan 250011, China)

Abstract:

DNA serves as the source of genetic information, and maintaining its integrity is crucial for the maintenance of cellular functions. DDR (DNA damage response) is a complex and sophisticated biological mecha nism evolved by cells to eliminate or repair DNA damage caused by endogenous and exogenous factors, ensuring the integrity and functionality of the genome. As an important sub-nuclear structure within the cell nucleus, para speckles are membrane-less nuclear organelles dynamically assembled through liquid-liquid phase separation of long non-coding RNAs and several RNA-binding proteins, playing a significant role in the maintenance of cellular homeostasis and functional repair. Research has revealed that paraspeckles are involved in the DDR process, ex erting important influences on the stages of DNA damage sensing, signal transduction, and repair, and are closely associated with carcinogenesis and cancer development. They can mediate the activation of p53 to regulate the ef f iciency of DDR, mediate cell cycle arrest and activate the DNA damage repair pathway to repair DNA damage. Their abnormal aggregation is closely related to chemotherapy resistance and radiotherapy resistance. This article systematically reviews the molecular mechanism of paraspeckles in regulating DDR, explores their role in carcino genesis and cancer development, and prospects the potential application of targeted paraspeckle regulation in cancer treatment.

CSTR: 32200.14.cjcb.2025.11.0020