Ppp4r1-KO Mouse

Ppp4r1, the protein phosphatase 4 regulatory subunit 1, is likely involved in various cellular regulatory processes related to protein phosphorylation, though its exact function details are yet to be fully elucidated. Phosphatase-related pathways are crucial in cells for controlling enzyme activity, signal transduction, and cell cycle progression [2].

In cancer research, studies on PPP4R1 have revealed its potential significance. In liver hepatocellular carcinoma (LIHC), its expression level is higher in cancerous tissues than adjacent tissues. PPP4R1 shows diagnostic value for 14 tumors (AUC > 0.7) based on ROC curves, and prognostic significance for five tumors. High expression of PPP4R1 is associated with poor prognosis, drug resistance (positive correlation with fludarabine's IC50), and may be related to natural killer cell-mediated toxicity in LIHC. A ceRNA network prediction indicated that the FGD5-AS1-hsa-miR-22-3p-PPP4R1 network could contribute to LIHC progression [2]. In thyroid carcinoma, lncRNA IGF2-AS may regulate the miR-500a-3p/PPP4R1/p-VEGFR2 signalling pathway to promote carcinoma progression and tubulogenesis [1]. Additionally, in a study of Arab-ancestry females, functional variants in PPP4R1 were associated with a higher migraine risk [3]. In breast cancers, downregulated expression of PPP4R1 was correlated with the luminal B molecular subtype [4]. In triploid Pacific oysters, a piRNA cluster was annotated with the PPP4R1 gene, which was downregulated in infertile female triploids [5].

In conclusion, PPP4R1 appears to be involved in multiple disease-related processes, especially in cancer where it shows potential as a diagnostic and prognostic biomarker, and in migraine as a gene associated with risk. Its role in oyster sterility also indicates its potential in non-mammalian biological systems. The study of PPP4R1 helps in understanding disease mechanisms and may offer new therapeutic targets [1,2,3,4,5].

References:

1. Xiang, Yuan, Zong, Qi-Bei, Liu, Hui, Li, Xing-Rui, Liao, Xing-Hua. . lncRNA IGF2-AS regulates miR-500a-3p/PPP4R1/p-VEGFR2 signalling pathway to promote thyroid carcinoma progression and tubulogenesis. In Clinical and translational medicine, 13, e1240. doi:10.1002/ctm2.1240. https://pubmed.ncbi.nlm.nih.gov/37070231/

2. Li, Xiaowei, Pan, Yinglian, Feng, Siren, Li, Mengsen, Zhu, Mingyue. 2024. The diagnostic, prognostic, drug sensitivity and ceRNA internet of PPP4R1 in liver hepatocellular carcinoma (LIHC). In Translational cancer research, 13, 594-612. doi:10.21037/tcr-23-1744. https://pubmed.ncbi.nlm.nih.gov/38482448/

3. Khan, Johra, Al Asoom, Lubna, Al Sunni, Ahmad, Banawas, Saeed, Borgio, J Francis. 2022. Whole-Exome Sequencing Reveals Migraine-Associated Novel Functional Variants in Arab Ancestry Females: A Pilot Study. In Brain sciences, 12, . doi:10.3390/brainsci12111429. https://pubmed.ncbi.nlm.nih.gov/36358356/

4. Addou-Klouche, Lynda, Adélaïde, José, Finetti, Pascal, Birnbaum, Daniel, Chaffanet, Max. 2010. Loss, mutation and deregulation of L3MBTL4 in breast cancers. In Molecular cancer, 9, 213. doi:10.1186/1476-4598-9-213. https://pubmed.ncbi.nlm.nih.gov/20698951/

5. Zhou, Yaru, Yu, Hong, Li, Qi, Liu, Shikai, Xu, Chengxun. 2024. Characterization of piRNAs in Diploid and Triploid Pacific Oyster Gonads: Exploring Their Potential Roles in Triploid Sterility. In Marine biotechnology (New York, N.Y.), 26, 1017-1029. doi:10.1007/s10126-024-10351-7. https://pubmed.ncbi.nlm.nih.gov/39073646/