Prrx2, the paired-related homeobox transcription factor, has been implicated in multiple biological processes. It participates in regulating gene expression and is associated with pathways like Wnt/β -catenin, TGF -β, and Hippo. Prrx2 is important in cell differentiation, proliferation, and in processes related to various diseases, making genetic models valuable for studying its functions [2,3,4,6,8,9].

Silencing Prrx2 in breast cancer cells inhibited their proliferation and growth in vitro and in vivo, and also down-regulated the Wnt/β -catenin signaling pathway, suggesting its oncogenic role in breast cancer [8]. In colon cancer, inhibition of Prrx2 reduced the invasive and migrating abilities of cells, hindered epithelial-mesenchymal transition (EMT), and suppressed liver metastasis through inactivation of the Wnt/β -catenin pathway [6]. Myoblast-derived exosomal Prrx2 enhanced osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) by transcriptionally regulating lncRNA-MIR22HG to activate the Hippo pathway, alleviating osteoporosis in mice [2]. In glioblastoma, circLRFN5 binds to Prrx2 protein and promotes its degradation, suppressing glioblastoma progression as Prrx2 transcriptionally upregulates GCH1, a ferroptosis suppressor [1]. In prostate cancer, activation of Prrx2 promoted enzalutamide resistance, and its expression was highest in double-negative prostate cancer, correlating with reduced overall survival [3]. In lung adenocarcinoma, Prrx2 was highly expressed, acting as a positive regulator of cell proliferation and a negative regulator of apoptosis by binding to the PSMD1 promoter [4]. Silencing Marveld3 upregulated Prrx2, which attenuated radiation-induced lipid peroxidation in skin cells, potentially protecting against radiation-induced ferroptosis [5]. In neuropathic pain, a spinal-specific super enhancer regulated chronic constriction injury-induced neuropathic pain by driving Prrx2 transcription in dorsal horn neurons, and knocking down Prrx2 alleviated neuropathic pain behaviors [7]. In odontoblast differentiation, Prrx2 may regulate pannexin 3 expression [10].

In conclusion, Prrx2 is involved in diverse biological functions such as cell proliferation, differentiation, and apoptosis. Through model-based research, its role in diseases like cancer, osteoporosis, radiation-induced skin injury, and neuropathic pain has been revealed. These findings provide insights into potential therapeutic targets for these diseases.