Slco4a1-KO Mouse

Slco4a1, solute carrier organic anion transporter family member 4A1, encodes OATP4A1, an uptake membrane transporter of metabolic products. It is involved in bile metabolism, organic anion transport, and ABC transport, and may influence various signaling pathways [5,7,9].

Research on Slco4a1 has mainly focused on its related long non-coding RNA, SLCO4A1-AS1. In lung cancer, SLCO4A1-AS1 reduces cancer cell migration and invasion by disrupting cytoskeleton filaments and antagonizes the TOX4/NTSR1 signaling axis [1]. In pancreatic cancer, its knockdown suppresses cell growth, migration, and invasion, and induces apoptosis, and it exerts an oncogenic function via the miR-4673/KIF21B axis [2]. In colorectal cancer, SLCO4A1-AS1 acts as an oncogene by regulating the Hsp90/Cdk2/c-Myc axis [3]. In laryngeal squamous cell carcinoma, silenced SLCO4A1-AS1 represses cell proliferation and facilitates apoptosis, acting as a ceRNA to upregulate SETD7 and activate the Wnt/β-catenin pathway [4]. In melanoma, down-regulation of SLCO4A1-AS1 weakens cell proliferation, migration, and invasion, and promotes apoptosis via the miR-1306-5p/PCGF2 axis [6]. In gastric cancer, overexpression of SLCO4A1-AS1 promotes cell viability, migration, and invasion, and suppresses apoptosis via the miR-149-5p/STAT3 axis [10].

Regarding Slco4a1 itself, in thyroid cancer, it is highly expressed, associated with cancer stage and poor progression-free survival, and involved in neutrophil-mediated immunity [5]. In colon adenocarcinoma, it is overexpressed, and high expression is linked to poor survival and negatively associated with the infiltrating levels of some immune cells [7]. In non-small cell lung cancer, it promotes cell proliferation, migration, and invasion, and is associated with the MAPK signaling pathway and tumor-infiltrating immune cells [8]. In high-grade serous ovarian cancer, higher SLCO4A1 expression is associated with inflammation-associated pathways [9].

In conclusion, Slco4a1 and its related lncRNA, SLCO4A1-AS1, play significant roles in multiple cancers, affecting cell proliferation, migration, invasion, apoptosis, and immune-related processes. The study of Slco4a1 and SLCO4A1-AS1 provides potential insights into cancer mechanisms and possible therapeutic targets.

References:

1. Chen, Yi-Ling, Liu, Yi-Nan, Lin, Yen-Ting, Wu, Huey-Dong, Shih, Jin-Yuan. 2023. LncRNA SLCO4A1-AS1 suppresses lung cancer progression by sequestering the TOX4-NTSR1 signaling axis. In Journal of biomedical science, 30, 80. doi:10.1186/s12929-023-00973-9. https://pubmed.ncbi.nlm.nih.gov/37726723/

2. Zhang, Jianxin, Shen, Yanbing, Ma, Dandan, Zhang, Zhiyong, Jin, Weidong. 2022. SLCO4A1-AS1 mediates pancreatic cancer development via miR-4673/KIF21B axis. In Open medicine (Warsaw, Poland), 17, 253-265. doi:10.1515/med-2022-0418. https://pubmed.ncbi.nlm.nih.gov/35233463/

3. Zhang, Jia, Cui, Kaisa, Huang, Liuying, Fei, Bojian, Huang, Zhaohui. 2022. SLCO4A1-AS1 promotes colorectal tumourigenesis by regulating Cdk2/c-Myc signalling. In Journal of biomedical science, 29, 4. doi:10.1186/s12929-022-00789-z. https://pubmed.ncbi.nlm.nih.gov/35039060/

4. Zhang, Feng, Mao, Dehong, He, Zhongmei, Zhang, Xu, Li, Linglong. 2021. SLCO4A1-AS1 regulates laryngeal squamous cell carcinoma cell phenotypes via the Wnt pathway. In Oral diseases, 29, 390-401. doi:10.1111/odi.13893. https://pubmed.ncbi.nlm.nih.gov/33914996/

5. Wang, Xin-Sheng, Wu, Shi-Le, Peng, Zhe, Zhu, Hai-Hong. 2021. SLCO4A1 is a Prognosis-Associated Biomarker Involved in Neutrophil-Mediated Immunity in Thyroid Cancer. In International journal of general medicine, 14, 9615-9628. doi:10.2147/IJGM.S339921. https://pubmed.ncbi.nlm.nih.gov/34924768/

6. Wang, Kai, Li, Min, Duan, Hongyan, Xu, Chengyang, Yu, Feifei. 2022. SLCO4A1-AS1 triggers the malignant behaviours of melanoma cells via sponging miR-1306-5p to enhance PCGF2. In Experimental dermatology, 31, 1220-1233. doi:10.1111/exd.14577. https://pubmed.ncbi.nlm.nih.gov/35427425/

7. Chen, Xiaolong, Yi, Gangfeng, Zhou, Yu, Han, Weilan, Wang, Fei. 2023. Prognostic Biomarker SLCO4A1 Is Correlated with Tumor Immune Infiltration in Colon Adenocarcinoma. In Mediators of inflammation, 2023, 4926474. doi:10.1155/2023/4926474. https://pubmed.ncbi.nlm.nih.gov/37124063/

8. Li, Shihao, Li, Zihao, Huang, Lan, Gu, Zhuoyu, Qi, Yu. 2024. SLCO4A1, as a novel prognostic biomarker of non‑small cell lung cancer, promotes cell proliferation and migration. In International journal of oncology, 64, . doi:10.3892/ijo.2024.5618. https://pubmed.ncbi.nlm.nih.gov/38275113/

9. Koller, Stephanie, Kendler, Jonatan, Karacs, Jasmine, Cacsire Castillo-Tong, Dan, Thalhammer, Theresia. 2022. SLCO4A1 expression is associated with activated inflammatory pathways in high-grade serous ovarian cancer. In Frontiers in pharmacology, 13, 946348. doi:10.3389/fphar.2022.946348. https://pubmed.ncbi.nlm.nih.gov/36105223/

10. Li, Qing, Zhang, Dachuan, Wang, Hui, Zheng, Xiao, Jiang, Jingting. 2021. SLCO4A1-AS1 Facilitates the Malignant Phenotype via miR-149-5p/STAT3 Axis in Gastric Cancer Cells. In Journal of oncology, 2021, 1698771. doi:10.1155/2021/1698771. https://pubmed.ncbi.nlm.nih.gov/34712324/