Osbpl5-KO Mouse

Osbpl5, short for oxysterol binding protein like 5, is involved in lipid metabolism and may play a role in phosphatidylinositol homeostasis. It has been associated with pathways such as the AMP-activated protein kinase (AMPK) signaling pathway, and is important in biological processes like cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) [1,2,3,5]. Genetic models can be used to study its functions.

In non-small cell lung cancer (NSCLC), knockdown of Osbpl5 suppressed cell proliferation, migration, invasion and the EMT process. It was also found to be a downstream target of miR-526b-3p, with lncRNA LMCD1-AS1 acting as a sponge for miR-526b-3p [1]. In transient cerebral ischemia, conditional knockout mice showed that Osbpl5 (through its relation with ORP5) contributed to the abnormal distribution of phosphatidylinositols and phosphatidylserine between the plasma membrane and endoplasmic reticulum, and abolishing the Osbpl5 gene significantly inhibited apoptosis and autophagy [3]. In ovarian cancer, knockdown of ARL4C reduced OSBPL5 expression through the Notch-RBP-Jκ-H3K4Me3 pathway, inhibiting cholesterol transport from lysosomes to the endoplasmic reticulum and leading to autophagy dysfunction, thus attenuating carboplatin resistance [4].

In summary, Osbpl5 is crucial in processes related to cell behavior and lipid metabolism. Model-based research, especially gene knockout studies in mice, has revealed its significant roles in diseases such as NSCLC, transient cerebral ischemia, and ovarian cancer, providing insights into potential therapeutic targets for these conditions.

References:

1. Hu, Rui, Yu, Yankai, Wang, Haining. 2022. The LMCD1-AS1/miR-526b-3p/OSBPL5 axis promotes cell proliferation, migration and invasion in non-small cell lung cancer. In BMC pulmonary medicine, 22, 30. doi:10.1186/s12890-022-01820-7. https://pubmed.ncbi.nlm.nih.gov/35000595/

2. Fan, Wen, Pan, Maoxing, Zheng, Chuiyang, Yang, Qinhe, Zhang, Yupei. 2024. Leonurine Inhibits Hepatic Lipid Synthesis to Ameliorate NAFLD via the ADRA1a/AMPK/SCD1 Axis. In International journal of molecular sciences, 25, . doi:10.3390/ijms251910855. https://pubmed.ncbi.nlm.nih.gov/39409181/

3. Shang, Fei-Fei, Luo, Li, Yan, Jianghong, He, Xiang, Liu, Wei. 2020. CircRNA_0001449 disturbs phosphatidylinositol homeostasis and AKT activity by enhancing Osbpl5 translation in transient cerebral ischemia. In Redox biology, 34, 101459. doi:10.1016/j.redox.2020.101459. https://pubmed.ncbi.nlm.nih.gov/32086008/

4. Yang, Juan, Peng, Shuping, Zhang, Keqiang. . ARL4C depletion suppresses the resistance of ovarian cancer to carboplatin by disrupting cholesterol transport and autophagy via notch-RBP-Jκ-H3K4Me3-OSBPL5. In Human & experimental toxicology, 41, 9603271221135064. doi:10.1177/09603271221135064. https://pubmed.ncbi.nlm.nih.gov/36366750/

5. Nagano, Kazuya, Imai, Sunao, Zhao, Xiluli, Tsutsumi, Yasuo, Tsunoda, Shin-Ichi. 2015. Identification and evaluation of metastasis-related proteins, oxysterol binding protein-like 5 and calumenin, in lung tumors. In International journal of oncology, 47, 195-203. doi:10.3892/ijo.2015.3000. https://pubmed.ncbi.nlm.nih.gov/25963840/