Rftn1-KO Mouse

Rftn1, also known as raftlin lipid raft linker 1, is involved in maintaining the integrity of lipid rafts. It may participate in immune responses or interact with the glucocorticoid receptor alpha and the androgen receptor, suggesting its importance in various biological processes [4].

In gastric cancer, knockdown of Rftn1 inhibited cell proliferation, induced cell cycle arrest in G0/G1 phase, promoted apoptosis, and inhibited the AKT signaling pathway while activating the p38 signaling pathway. Conversely, overexpression had the opposite effects. Cell derived xenograft experiments also showed that knockdown of Rftn1 inhibited GC cell growth in vivo, indicating its oncogenic role in gastric cancer [1].

In acute pancreatitis, the tryptophan metabolite norharman increased the transcription level of Rftn1 by inhibiting histone deacetylase (HDACs) activity, which in turn inhibited M1 macrophages' activation, restored lipid metabolism balance, and relieved multiple inflammatory responses [2].

In chronic suppurative otitis media (CSOM), Rftn1 was highly expressed. Inhibition of Rftn1 reduced the inflammatory response and suppressed lipid raft formation, also reducing the expression of TLR4. Lactobacillus alleviated CSOM progression by reducing Rftn1 and TLR4 expression [3].

In conclusion, Rftn1 plays crucial roles in maintaining lipid raft integrity and is involved in immune-related and cell-growth-related biological processes. Studies using gene knockdown models in diseases such as gastric cancer, acute pancreatitis, and CSOM have revealed its functions in promoting cancer cell growth and regulating inflammatory responses, providing potential prognostic and therapeutic targets for these diseases.

References:

1. Deng, Chaowei, Zhang, Lu, Ma, Xiaoping, Jia, Yuzhen, Zhao, Lingyu. 2022. RFTN1 facilitates gastric cancer progression by modulating AKT/p38 signaling pathways. In Pathology, research and practice, 234, 153902. doi:10.1016/j.prp.2022.153902. https://pubmed.ncbi.nlm.nih.gov/35490655/

2. Zhou, Qi, Tao, Xufeng, Guo, Fangyue, Shang, Dong, Xiang, Hong. 2023. Tryptophan metabolite norharman secreted by cultivated Lactobacillus attenuates acute pancreatitis as an antagonist of histone deacetylases. In BMC medicine, 21, 329. doi:10.1186/s12916-023-02997-2. https://pubmed.ncbi.nlm.nih.gov/37635214/

3. Liu, Zhuohui, Zhang, Fan, Jia, Fengfeng, Ruan, Biao, Long, Ruiqing. 2024. Lactobacillus Protects Against Chronic Suppurative Otitis Media via Modulating RFTN1/ Lipid Raft /TLR4-Mediated Inflammation. In Biologics : targets & therapy, 18, 453-468. doi:10.2147/BTT.S484410. https://pubmed.ncbi.nlm.nih.gov/39742136/

4. Li, Meng, Chen, Ying, Yao, Jianhua, Zhao, Shancen, Zhu, Zhouhai. 2020. Genome-Wide Association Study of Smoking Behavior Traits in a Chinese Han Population. In Frontiers in psychiatry, 11, 564239. doi:10.3389/fpsyt.2020.564239. https://pubmed.ncbi.nlm.nih.gov/33033484/