Nrip3-KO Mouse

NRIP3, also known as nuclear receptor interacting protein 3, is a gene involved in multiple biological processes. It has been implicated in various signaling pathways, and its function appears to be significant in cancer-related processes. Genetic models, such as gene knockout mouse models, can potentially offer insights into its exact role in normal and diseased states.

In colorectal cancer (CRC), NRIP3 methylation was found in 50.6% of CRC samples, 32.2% of colorectal adenomatous polyps, and 2.7% of resected margin samples from CRC tissue. NRIP3 methylation was associated with late-onset, poor tumor differentiation, lymph node metastasis, and poor 5-year overall survival, and was an independent poor prognostic marker. NRIP3 inhibited cell proliferation, colony formation, invasion, and migration, while inducing G1/S arrest and suppressing CRC growth by inhibiting PI3K-AKT signaling both in vitro and in vivo. Additionally, NRIP3 methylation sensitized CRC cells to combined PI3K and ATR/ATM inhibitors [1].

In esophageal squamous cell carcinoma (ESCC), NRIP3 promoted tumor cell growth and resistance to chemoradiotherapy by increasing and binding to DDI1 and RTF2, and accelerating the removal of RTF2. Elevated NRIP3 was associated with poor clinical outcomes in ESCC patients receiving radiotherapy and/or cisplatin-based chemotherapy [2].

In MYCN-amplified neuroblastoma cells, depletion of L3MBTL2, which normally silences NRIP3, suppressed cell proliferation via cell-cycle arrest and gamma-H2A.X upregulation, and profoundly suppressed xenograft tumor formation [3].

In conclusion, NRIP3 appears to play a crucial role in cancer development and response to treatment. In CRC, its methylation status is related to prognosis and treatment sensitivity, while in ESCC, it promotes resistance to chemoradiotherapy. In neuroblastoma, its regulation by L3MBTL2 affects cell proliferation. These findings from model-based research, including in vivo studies, help understand the complex biological functions of NRIP3 in cancer-related processes.

References:

1. Zhang, Meiying, Li, Xiaoyun, Herman, James G, He, Kunlun, Guo, Mingzhou. 2024. Methylation of NRIP3 Is a Synthetic Lethal Marker for Combined PI3K and ATR/ATM Inhibitors in Colorectal Cancer. In Clinical and translational gastroenterology, 15, e00682. doi:10.14309/ctg.0000000000000682. https://pubmed.ncbi.nlm.nih.gov/38235705/

2. Suo, Daqin, Wang, Ling, Zeng, Tingting, Guan, Xin-Yuan, Li, Yan. 2020. NRIP3 upregulation confers resistance to chemoradiotherapy in ESCC via RTF2 removal by accelerating ubiquitination and degradation of RTF2. In Oncogenesis, 9, 75. doi:10.1038/s41389-020-00260-4. https://pubmed.ncbi.nlm.nih.gov/32839439/

3. Okada, Ryu, Takenobu, Hisanori, Satoh, Shunpei, Ohira, Miki, Kamijo, Takehiko. 2024. L3MBTL2 maintains MYCN-amplified neuroblastoma cell proliferation through silencing NRIP3 and BRME1 genes. In Genes to cells : devoted to molecular & cellular mechanisms, 29, 838-853. doi:10.1111/gtc.13148. https://pubmed.ncbi.nlm.nih.gov/39189159/