RNA-binding protein quaking: a multifunctional regulator in tumour progression

• Published in: Annals of medicine (Helsinki) 2025-12, Vol.57 (1), p.2443046
• Main Authors: Zhu, Wangyu, Yang, Weiwei, Sun, Guoping, Huang, Jian
• Format: Article
• Language: English
• Subjects: Alternative Splicing; Disease Progression; Gene Expression Regulation, Neoplastic; Humans; Neoplasms - genetics; Neoplasms - metabolism; Neoplasms - pathology; Oncology; post-translational regulation; QKI; Review; RNA, Messenger - metabolism; RNA-Binding Proteins - genetics; RNA-Binding Proteins - metabolism; Signal Transduction - genetics; Tumor Microenvironment - genetics; tumour progression
• ISSN: 0785-3890; 1365-2060; 1365-2060
• DOI: 10.1080/07853890.2024.2443046

Quaking (QKI) is a member of the signal transduction and activators of RNA (STAR) family, performing a crucial multifunctional regulatory role in alternative splicing, mRNA precursor processing, mRNA transport and localization, mRNA stabilization, and translation during tumour progression. Abnormal QKI expression or fusion mutations lead to aberrant RNA and protein expression, thereby promoting tumour progression. However, in many types of tumour, QKI played a role as tumour suppressor, the regulatory role of QKI in tumour progression remains ambiguous. This review aims to analyze the isoform and function of QKI, the impact of QKI-regulated gene expression or signalling pathway alterations on tumour progression, and its potential clinical applications as a predictive marker or target for tumour therapy. We reviewed recent studies and summarized the function of QKI alteration in tumour progression. QKI mediate post-transcriptional gene regulation including alternative splicing, polyadenylation, mRNA stabilization, mRNA subcellular location, and noncoding RNA by binding to the QRE elements of targeted nucleotide. The dysregulation of QKI is intricately correlated to tumour proliferation, metastasis, angiogenesis, tumor stem cells, the tumour microenvironment, and treatment sensitivity, and represents as a potential biological predictor in tumour diagnosis and prognosis. QKI play a critical role as tumour suppressor or an oncogene in tumour progression due to the different splicing sites and transcripts with various tumour subtype or tumor micorenvironment. Ongoing research about QKI's functions and mechanisms persist is required to conduct for better understanding the role of QKI in tumour regulation.