Prr11-KO Mouse

Prr11, or Proline rich 11, is a protein-coding gene located on chromosome 17q22-23. Initially associated with cell-cycle progression, it has now been found to play critical roles in multiple cellular processes such as proliferation, colony formation, migration, invasion, apoptosis, autophagy, and chemotherapy resistance. It exerts these functions via multiple signaling pathways and biological molecules in various solid tumors, making it an important gene in cancer research [1].

In glioblastoma, depletion of Prr11 sensitizes cells to temozolomide by inducing ferroptosis. Prr11 binds to and stabilizes dihydroorotate dehydrogenase (DHODH), leading to ferroptosis-resistant glioma. Down-regulating Prr11 increases lipid peroxidation and alters DHODH-mediated mitochondrial morphology, enhancing chemotherapy sensitivity [2].

In clear cell renal cell carcinoma (ccRCC), Prr11 silencing reduces cell proliferation and migration. Prr11 induces E2F1 protein degradation, affecting cell-cycle progression, and is a target gene of c-Myc, which promotes ccRCC progression [3].

In bladder urothelial carcinoma, Prr11 is highly expressed, and its high expression is associated with poor outcomes and correlates with tumor mutational burden and immune cell infiltration [4].

In early pregnancy, low expression of Prr11 in placental villous tissues from early pregnancy loss (EPL) patients was observed. Overexpression of Prr11 promotes the motility of trophoblast cells by binding to the ARP2/3 complex [5].

In pan-cancer, interfering with Prr11 inhibits cell proliferation and migration. Prr11 interacts with E2F1 on the PTTG1 promoter region to increase PTTG1 expression, influencing cell-cycle progression [6].

In colorectal cancer, Prr11 silencing suppresses cell proliferation, invasion, and migration, as well as tumor growth, by inhibiting the EGFR/ERK/AKT pathway via restraining CTHRC1 expression [7].

In pancreatic cancer, high protein expression of Prr11 is associated with adverse clinicopathological features and shorter overall survival [8].

In glioma, Prr11 is a reliable predictor in diagnosis and prognosis, positively correlates with malignancy, and knockdown of Prr11 suppresses cell viability, migration, and cell-cycle progression, while inducing apoptosis and autophagy [9].

In non-small cell lung cancer cells, Prr11 recruits the ARP2/3 complex to promote filopodia formation, focal adhesion turnover, and cell motility [10].

In conclusion, Prr11 is a multifunctional gene involved in various biological processes, especially those related to cell growth, movement, and survival. Its dysregulation is associated with multiple diseases, particularly cancers. Loss-of-function experiments, though not always in KO/CKO mouse models but also in cell-based studies, have revealed its oncogenic roles in different cancer types, providing potential targets for cancer therapies.

References:

1. Han, Wei, Chen, Liang. 2022. PRR11 in Malignancies: Biological Activities and Targeted Therapies. In Biomolecules, 12, . doi:10.3390/biom12121800. https://pubmed.ncbi.nlm.nih.gov/36551227/

2. Miao, Zong, Xu, Lei, Gu, Wei, Ji, Jing, Chen, Juxiang. 2024. A targetable PRR11-DHODH axis drives ferroptosis- and temozolomide-resistance in glioblastoma. In Redox biology, 73, 103220. doi:10.1016/j.redox.2024.103220. https://pubmed.ncbi.nlm.nih.gov/38838551/

3. Chen, Siming, He, Zhiwen, Peng, Tianchen, Xiao, Yu, Wang, Xinghuan. 2021. PRR11 promotes ccRCC tumorigenesis by regulating E2F1 stability. In JCI insight, 6, . doi:10.1172/jci.insight.145172. https://pubmed.ncbi.nlm.nih.gov/34499617/

4. Ni, Wenpeng, Yi, Lijuan, Dong, Xiaoru, Wei, Qingling, Yuan, Chunlei. 2023. PRR11 is a prognostic biomarker and correlates with immune infiltrates in bladder urothelial carcinoma. In Scientific reports, 13, 2051. doi:10.1038/s41598-023-29316-2. https://pubmed.ncbi.nlm.nih.gov/36739300/

5. Zhu, Pengfei, Dou, Chengli, Song, Zhijiao, Wu, Xueqing, Miao, Yiliang. . ELF1/PRR11/ARP2/3 promoted trophoblast cells proliferation and motility in early pregnancy. In American journal of reproductive immunology (New York, N.Y. : 1989), 90, e13758. doi:10.1111/aji.13758. https://pubmed.ncbi.nlm.nih.gov/37641376/

6. Zhang, Haibo, He, Ziqing, Qiu, Li, Lin, Shudai, Du, Hongli. 2022. PRR11 promotes cell proliferation by regulating PTTG1 through interacting with E2F1 transcription factor in pan-cancer. In Frontiers in molecular biosciences, 9, 877320. doi:10.3389/fmolb.2022.877320. https://pubmed.ncbi.nlm.nih.gov/36060253/

7. Ma, Hualing, Yang, Weigui, Wang, Xiufang, Dai, Gang. . PRR11 Promotes Proliferation and Migration of Colorectal Cancer through Activating the EGFR/ERK/AKT Pathway via Increasing CTHRC1. In Annals of clinical and laboratory science, 52, 86-94. doi:. https://pubmed.ncbi.nlm.nih.gov/35181621/

8. Olsson Hau, Sofie, Wahlin, Sara, Cervin, Sophie, Karnevi, Emelie, Jirström, Karin. 2021. PRR11 unveiled as a top candidate biomarker within the RBM3-regulated transcriptome in pancreatic cancer. In The journal of pathology. Clinical research, 8, 65-77. doi:10.1002/cjp2.238. https://pubmed.ncbi.nlm.nih.gov/34379360/

9. Han, Wei, Chen, Liang. 2023. Predictive significance of PRR11 in prognosis and immune infiltration of glioma patients. In Molecular carcinogenesis, 62, 975-990. doi:10.1002/mc.23539. https://pubmed.ncbi.nlm.nih.gov/37036189/

10. Wei, Zhili, Wang, Ru, Yin, Xun, Jin, Guoxiang, Zhang, Chundong. 2021. PRR11 induces filopodia formation and promotes cell motility via recruiting ARP2/3 complex in non-small cell lung cancer cells. In Genes & diseases, 9, 230-244. doi:10.1016/j.gendis.2021.02.012. https://pubmed.ncbi.nlm.nih.gov/35005120/