Yu Shiyi, Jiang Chengyang, Yang Yawen, Cheng Fei, Liu Fangchen, Liu Chang, Gong Xue
Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou, Jiangsu, China.
Jiangsu Key Laboratory of Experimental & Translational Non-Coding RNA Research, Yangzhou University, Yangzhou, Jiangsu, China.
Mol Med. 2025 Jan 22;31(1):20. doi: 10.1186/s10020-025-01087-8.
Proteins that bind to DNA/RNA are typically evolutionarily conserved with multiple regulatory functions in transcription initiation, mRNA translation, stability of RNAs, and RNA splicing. Therefore, dysregulation of DNA/RNA binding proteins such as purine-rich element binding protein alpha (PURα) disrupts signaling transduction and often leads to human diseases including cancer. PURα was initially recognized as a tumor suppressor in acute myeloid leukemia (AML) and prostate cancer (PC). Most recently, several studies have revealed that PURα is dysregulated in multiple cancers, such as breast cancer (BC) and esophageal squamous cell carcinoma (ESCC). The oncogenic or tumor-suppressive functions of PURα are realized via regulating RNA/protein interaction, mRNA translation, formation of stress granules (SGs), and transcriptional regulation of several oncogenes and tumor suppressors. Although DNA/RNA binding proteins are hardly targeted, novel strategies have been applied to identify compounds targeting PURα and have demonstrated promising anti-tumor efficacy in the preclinical study. The present review summarizes the most recently discovered critical roles of PURα in various cancer types, providing an overview of the biomarker and therapeutic target potential of PURα for patients with cancer.
与DNA/RNA结合的蛋白质通常在进化上是保守的，在转录起始、mRNA翻译、RNA稳定性和RNA剪接中具有多种调节功能。因此，诸如富含嘌呤元件结合蛋白α（PURα）等DNA/RNA结合蛋白的失调会破坏信号转导，并常常导致包括癌症在内的人类疾病。PURα最初被认为是急性髓系白血病（AML）和前列腺癌（PC）中的一种肿瘤抑制因子。最近，几项研究表明，PURα在多种癌症中失调，如乳腺癌（BC）和食管鳞状细胞癌（ESCC）。PURα的致癌或肿瘤抑制功能是通过调节RNA/蛋白质相互作用、mRNA翻译、应激颗粒（SGs）的形成以及几种癌基因和肿瘤抑制因子的转录调控来实现的。尽管DNA/RNA结合蛋白很难成为靶点，但已应用新策略来鉴定靶向PURα的化合物，并在临床前研究中显示出有前景的抗肿瘤疗效。本综述总结了PURα在各种癌症类型中最近发现的关键作用，概述了PURα作为癌症患者生物标志物和治疗靶点的潜力。
