Prpf4b-flox Mouse

Prpf4b, also known as PRP4K, is an essential kinase conserved from amoebae to animals. It is involved in pre-mRNA splicing, where it interacts with and phosphorylates PRPF6 and PRPF31 during spliceosomal assembly to facilitate the formation of the spliceosome B complex. Additionally, it participates in regulating transcription and the spindle assembly checkpoint, contributing to tumour suppression and responses to chemotherapy [5].

In cancer research, reduced Prpf4b expression is associated with aggressive breast and ovarian cancer phenotypes. In non-transformed mammary epithelial cell lines, depletion of Prpf4b by shRNA either reduced or had no effect on 2D migration but increased invasive potential in 3D transwell assays. In mesenchymal triple-negative breast cancer cells, its depletion enhanced both 2D migration and 3D invasion. Also, induction of EMT in MCF10A cells led to significantly reduced Prpf4b expression [6]. In colon cancer, the phosphorylation level of PRPF4BS431 was significantly correlated with the overall survival of patients [1]. In lung adenocarcinoma, miR-224 was found to regulate Prpf4b, and their expressions were significantly negatively correlated, with both being associated with lymph node metastasis and prognosis [2]. In hepatocellular carcinoma, miR-371-5p down-regulates Prpf4b, and over-expression of miR-371-5p and knockdown of Prpf4b promote cell growth by accelerating the G1/S transition [3]. In triple-negative breast cancer, Prpf4b is essential for cancer cell migration, amplified in human primary breast tumours and associated with metastasis-free survival, and its depletion down-regulates genes involved in focal adhesion and ECM-interaction pathways [4].

In conclusion, Prpf4b is crucial for pre-mRNA splicing and has diverse functions in multiple cellular pathways. Its dysregulation is implicated in various cancers, including breast, ovarian, colon, lung adenocarcinoma, and hepatocellular carcinoma. Research on Prpf4b, especially through loss-of-function experiments in cell lines, has enhanced our understanding of cancer-related biological processes, offering potential targets for cancer therapy.