PRRX2, the paired-related homeobox transcription factor, is involved in multiple biological processes and disease-related pathways. It can participate in regulating gene transcription, and is associated with pathways like Wnt/β-catenin, Hippo, and is related to ferroptosis, cell proliferation, apoptosis, invasion, and migration. Genetic models can be used to study its functions in different biological contexts [1-10].

In glioblastoma, circLRFN5 binds to PRRX2 protein, promoting its degradation via a ubiquitin-mediated proteasomal pathway. PRRX2 can transcriptionally upregulate GCH1 expression, which is a ferroptosis suppressor [1]. In osteoporosis, myoblast-derived exosomal Prrx2 enhances osteogenic differentiation of BMSCs by transcriptionally regulating lncRNA-MIR22HG to activate the Hippo pathway [2]. In prostate cancer, activation of PRRX2 promotes enzalutamide resistance, and it is related to alterations in the CDK4/6/Rb/E2F and BCL2 pathways [3]. In lung adenocarcinoma, PRRX2 is highly expressed, acts as a positive regulator of cell proliferation and a negative regulator of apoptosis, and can bind with the PSMD1 promoter to regulate its expression [4]. In skin cells, silencing Marveld3 upregulates PRRX2, which may attenuate radiation-induced lipid peroxidation [5]. In colon cancer, inhibition of PRRX2 reduces invasive and migrating abilities, hinders epithelial-mesenchymal transition (EMT), and suppresses liver metastasis through inactivation of the Wnt/β-catenin pathway [6]. In breast cancer, silencing Prrx2 expression inhibits cell proliferation and tumor growth, and down-regulates the activity of the Wnt/β-catenin signaling pathway [7]. Overexpression of PRRX2 in mammary epithelial cells enhances invasion, migration, and induces partial EMT [8]. In tooth development, Prrx2 may regulate Panx3 expression during odontoblastic differentiation [9].

In conclusion, PRRX2 plays crucial roles in various biological processes and disease conditions. Through gene-based research models, we've learned that it impacts processes like ferroptosis, osteogenic differentiation, cancer cell behaviors (such as proliferation, invasion, and drug resistance), and tooth development. These findings provide insights into disease mechanisms and potential therapeutic targets related to Prrx2-associated pathways.

References:

1. Jiang, Yang, Zhao, Junshuang, Li, Rongqing, Gao, Liang, Cui, Daming. 2022. CircLRFN5 inhibits the progression of glioblastoma via PRRX2/GCH1 mediated ferroptosis. In Journal of experimental & clinical cancer research : CR, 41, 307. doi:10.1186/s13046-022-02518-8. https://pubmed.ncbi.nlm.nih.gov/36266731/

2. Li, Yunchao, Wang, Xiaoxiao, Pan, Changyu, Chen, Zejun, He, Haoyu. 2023. Myoblast-derived exosomal Prrx2 attenuates osteoporosis via transcriptional regulation of lncRNA-MIR22HG to activate Hippo pathway. In Molecular medicine (Cambridge, Mass.), 29, 54. doi:10.1186/s10020-023-00649-y. https://pubmed.ncbi.nlm.nih.gov/37081396/

3. Rodríguez, Yara, Unno, Kenji, Truica, Mihai I, Han, Huiying, Abdulkadir, Sarki A. . A Genome-Wide CRISPR Activation Screen Identifies PRRX2 as a Regulator of Enzalutamide Resistance in Prostate Cancer. In Cancer research, 82, 2110-2123. doi:10.1158/0008-5472.CAN-21-3565. https://pubmed.ncbi.nlm.nih.gov/35405009/

4. Liu, Lihua, Liu, Aihua, Liu, Xuezheng. 2022. PRRX2 predicts poor survival prognosis, and promotes malignant phenotype of lung adenocarcinoma via transcriptional activates PSMD1. In Translational oncology, 27, 101586. doi:10.1016/j.tranon.2022.101586. https://pubmed.ncbi.nlm.nih.gov/36379103/

5. Cao, Jinming, Wu, Mengyao, Mo, Wei, Zhang, Bin, Cao, Jianping. 2024. Upregulation of PRRX2 by silencing Marveld3 as a protective mechanism against radiation-induced ferroptosis in skin cells. In Molecular medicine (Cambridge, Mass.), 30, 182. doi:10.1186/s10020-024-00958-w. https://pubmed.ncbi.nlm.nih.gov/39434056/

6. Chai, Wen-Xiao, Sun, Li-Guo, Dai, Fu-Hong, Zheng, Ning-Gang, Cai, Hong-Yi. 2019. Inhibition of PRRX2 suppressed colon cancer liver metastasis via inactivation of Wnt/β-catenin signaling pathway. In Pathology, research and practice, 215, 152593. doi:10.1016/j.prp.2019.152593. https://pubmed.ncbi.nlm.nih.gov/31471104/

7. Lü, Z D, Yang, Z C, Jin, L Y, Kong, B, Wang, H B. . [Effects of Prrx2 gene silencing on the proliferation of breast cancer and its molecular mechanisms]. In Zhonghua yi xue za zhi, 100, 942-946. doi:10.3760/cma.j.cn112137-20190710-01309. https://pubmed.ncbi.nlm.nih.gov/32234171/

8. Juang, Yu-Lin, Jeng, Yung-Ming, Chen, Chi-Long, Lien, Huang-Chun. 2016. PRRX2 as a novel TGF-β-induced factor enhances invasion and migration in mammary epithelial cell and correlates with poor prognosis in breast cancer. In Molecular carcinogenesis, 55, 2247-2259. doi:10.1002/mc.22465. https://pubmed.ncbi.nlm.nih.gov/26824226/

9. Tanaka, Manami, Sugimoto, Asuna, Iwata, Kokoro, Oishi, Atsushi, Iwamoto, Tsutomu. 2024. Prrx2, the paired-related homeobox transcription factor, functions as a potential regulator of pannexin 3 expression in odontoblast differentiation. In Journal of oral biosciences, 67, 100601. doi:10.1016/j.job.2024.100601. https://pubmed.ncbi.nlm.nih.gov/39733924/