Prr11-KO Mouse

Prr11, or Proline rich 11, is a proline-rich protein coding gene located on chromosome 17q22-23. Initially known for its relation to cell-cycle progression, it has a crucial impact on multiple cellular processes such as proliferation, colony formation, migration, invasion, apoptosis, autophagy, and chemotherapy resistance through various signaling pathways in several solid tumors [1].

In glioblastoma, depletion of Prr11 significantly sensitizes cells to temozolomide by inducing ferroptosis. Prr11 binds to and stabilizes dihydroorotate dehydrogenase (DHODH), and down-regulating Prr11 increases lipid peroxidation, promoting ferroptosis and TMZ 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 [3]. In bladder urothelial carcinoma, high Prr11 expression is associated with poor outcomes and correlates with tumor mutational burden and immune cell infiltration [4]. In early pregnancy, overexpression of Prr11 promotes the proliferation and migration of trophoblast cells [5]. In pan-cancer, interfering with Prr11 inhibits cell proliferation and migration, and Prr11 influences the cell cycle by regulating PTTG1 through interacting with E2F1 [6]. In colorectal cancer, Prr11 silencing suppresses cell proliferation, invasion, and migration by inhibiting the EGFR/ERK/AKT pathway via restraining CTHRC1 expression [7]. In pancreatic cancer, high Prr11 protein expression is associated with adverse clinicopathological features and shorter overall survival [8]. In glioma, Prr11 is a promising predictor for diagnosis and prognosis, and its knockdown suppresses cell viability, migration, and cell-cycle progression, and induces apoptosis and autophagy [9]. In non-small cell lung cancer, Prr11 recruits the ARP2/3 complex to promote filopodia formation, focal adhesion turnover, and cell motility [10].

In summary, Prr11 is a key gene involved in multiple cellular functions and plays significant roles in various malignancies. The findings from loss-of-function experiments in different cancer cell lines, as well as in-vitro and in-vivo models, have revealed its importance in cancer progression, making it a potential target for cancer therapy.

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/