DNA损伤修复相关RBP在前列腺癌恶性进展中的作用与分子机制研究
Study on the Roles and Molecular Mechanisms of DNA Damage Repair-Related RBPs in the Malignant Progression of Prostate Cancer
尚晓艺 1张元祯 1邹成 1张定校1
作者信息
- 1. 湖南大学生命医学交叉研究院，长沙 410082
- 折叠
摘要
前列腺癌（Prostate cancer，PCa）是老年男性最高发的恶性肿瘤之一。针对晚期前列腺癌患者对雄激素剥夺疗法（ADT）易产生耐药性、治疗效果不佳的问题，挖掘恶性前列腺癌新的治疗靶点刻不容缓。方法：首先采用生物信息学分析方法，探究RNA结合蛋白（RBP）表达失调与前列腺癌恶性进展的关联，分析不同病理阶段RBP的表达差异及与DNA损伤修复相关RBP在去势抵抗性前列腺癌中的表达情况。之后，借助Uniport数据库明确关键RNA结合蛋白的功能结构域，通过多数据集交叉验证，筛选确定核心研究对象（POLQ及BLM两个RBP）。最后，通过体外表型实验，验证敲低与DNA损伤修复相关的RBP对前列腺癌细胞恶性生物学行为的影响。结果：敲低与DNA损伤修复相关的RBP能显著抑制前列腺癌细胞的增殖与迁移。结论：本研究发现了POLQ及BLM两个RBP在前列腺癌晚期中表达上调，抑制这两个RBP能够显著遏制前列腺癌细胞的增殖与迁移，为晚期前列腺癌（尤其是去势抵抗性前列腺癌）的诊断、治疗方案优化提供了新的理论依据与研究思路。
Abstract
Prostate cancer (PCa) is one of the most common malignant tumors in elderly men. Since patients with advanced prostate cancer are prone to developing resistance to androgen deprivation therapy (ADT), resulting in poor therapeutic outcomes, it is urgent to identify new therapeutic targets for aggressive prostate cancer.Methods: First, bioinformatics analyses were performed to investigate the association between dysregulated RNA-binding protein (RBP) expression and the malignant progression of prostate cancer, including the differential expression of RBPs across different pathological stages and the expression patterns of DNA damage repair-related RBPs in castration-resistant prostate cancer. Next, the functional domains of key RNA-binding proteins were identified using the UniProt database, and cross-validation across multiple datasets was conducted to screen and determine the core research targets, namely POLQ and BLM. Finally, in vitro phenotypic experiments were carried out to verify the effects of knocking down DNA damage repair-related RBPs on the malignant biological behaviors of prostate cancer cells.Results: Knockdown of DNA damage repair-related RBPs significantly inhibited the proliferation and migration of prostate cancer cells.Conclusion: This study found that the two RBPs, POLQ and BLM, were upregulated in advanced prostate cancer. Inhibition of these two RBPs could markedly suppress the proliferation and migration of prostate cancer cells, providing new theoretical evidence and research directions for the diagnosis of advanced prostate cancer, especially castration-resistant prostate cancer, and for the optimization of its treatment strategies.关键词
前列腺癌/RNA结合蛋白/DNA损伤修复/POLQ/BLMKey words
Prostate cancer/RNA-binding proteins/DNA damage repair/POLQ/BLM引用本文复制引用
尚晓艺,张元祯,邹成,张定校.DNA损伤修复相关RBP在前列腺癌恶性进展中的作用与分子机制研究[EB/OL].(2026-03-23)[2026-03-25].http://www.paper.edu.cn/releasepaper/content/202603-212.学科分类
生物科学研究方法、生物科学研究技术/生物科学现状、生物科学发展
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