Olr1-KO Mouse

Olr1, also known as oxidized LDL receptor 1, encodes LOX-1, LOXIN, and OLR1D4 transcript variants. It is a lectin-like scavenger receptor that recognizes ligands such as oxidized low-density lipoprotein (ox-LDL). OLR1 is involved in multiple biological processes, especially those related to cardiovascular and metabolic disorders [2,3]. In the cardiovascular system, it is associated with pathways leading to atherosclerotic plaque formation [3].

In cancer research, OLR1 shows significant implications. In pancreatic cancer, OLR1 promotes cell proliferation and metastasis both in vitro and in vivo by increasing HMGA2 transcription via upregulating c-Myc expression, and patients with high expression of the OLR1-c-Myc-HMGA2 axis have a worse prognosis [5]. In head and neck squamous cell carcinoma (HNSCC), OLR1 is highly expressed in tumors, related to advanced clinicopathological factors and unfavorable outcomes. High OLR1 expression is associated with immune escape and less benefit from immune checkpoint inhibitor therapy, and may affect epithelial-mesenchymal transition (EMT), stemness, and cuproptosis resistance [1,6]. In esophageal cancer, OLR1 suppresses autophagic cell death through the MAP2K/MEK-MAPK/ERK-TFEB pathway to promote tumorigenesis [7]. In addition, OLR1 gene polymorphisms are associated with the risk of coronary artery disease (CAD), and specific SNPs like rs1050283 and rs3736235 in the haplotype block are more significantly related to CAD risk [2]. There is also an association between OLR1 gene variations and polycystic ovary syndrome (PCOS) as well as atherosclerotic risk factors [4].

In conclusion, OLR1 is a multifunctional gene involved in both cardiovascular and cancer-related biological processes. Studies on OLR1, especially through in vivo models in cancer and genetic polymorphism analysis in cardiovascular diseases, have revealed its role in disease development, providing potential targets for treatment in these disease areas.

References:

1. Wu, Lei, Liu, Yuantong, Deng, Weiwei, Bu, Linlin, Chen, Lei. 2023. OLR1 Is a Pan-Cancer Prognostic and Immunotherapeutic Predictor Associated with EMT and Cuproptosis in HNSCC. In International journal of molecular sciences, 24, . doi:10.3390/ijms241612904. https://pubmed.ncbi.nlm.nih.gov/37629087/

2. Salehipour, Pouya, Rezagholizadeh, Farzaneh, Mahdiannasser, Mojdeh, Kazerani, Reihane, Modarressi, Mohammad Hossein. 2021. Association of OLR1 gene polymorphisms with the risk of coronary artery disease: A systematic review and meta-analysis. In Heart & lung : the journal of critical care, 50, 334-343. doi:10.1016/j.hrtlng.2021.01.015. https://pubmed.ncbi.nlm.nih.gov/33524863/

3. Pirillo, Angela, Norata, Giuseppe Danilo, Catapano, Alberico Luigi. 2013. LOX-1, OxLDL, and atherosclerosis. In Mediators of inflammation, 2013, 152786. doi:10.1155/2013/152786. https://pubmed.ncbi.nlm.nih.gov/23935243/

4. Sahin, Serap Baydur, Nalkiran, Ihsan, Ayaz, Teslime, Calapoglu, Tugba, Sevim Nalkiran, Hatice. 2023. Genetic variations in OLR1 gene associated with PCOS and atherosclerotic risk factors. In Journal of investigative medicine : the official publication of the American Federation for Clinical Research, 71, 113-123. doi:10.1177/10815589221141831. https://pubmed.ncbi.nlm.nih.gov/36647317/

5. Yang, Gang, Xiong, Guangbing, Feng, Mengyu, Zhang, Taiping, Zhao, Yupei. 2020. OLR1 Promotes Pancreatic Cancer Metastasis via Increased c-Myc Expression and Transcription of HMGA2. In Molecular cancer research : MCR, 18, 685-697. doi:10.1158/1541-7786.MCR-19-0718. https://pubmed.ncbi.nlm.nih.gov/32019809/

6. Zhang, Peng, Zhao, Yan, Xia, Xin, Yu, Shuting, Chen, Xingming. 2023. Expression of OLR1 gene on tumor-associated macrophages of head and neck squamous cell carcinoma, and its correlation with clinical outcome. In Oncoimmunology, 12, 2203073. doi:10.1080/2162402X.2023.2203073. https://pubmed.ncbi.nlm.nih.gov/37089448/

7. Li, Can, Wang, Lan. 2021. TFEB-dependent autophagy is involved in scavenger receptor OLR1/LOX-1-mediated tumor progression. In Autophagy, 18, 462-464. doi:10.1080/15548627.2021.2012970. https://pubmed.ncbi.nlm.nih.gov/34936535/