Slc29a1, also known as equilibrative nucleoside transporter 1 (ENT1), is a crucial gene encoding a membrane transporter. It is involved in the transportation of nucleoside analogs, such as cytosine arabinoside (AraC), and plays a role in maintaining nicotinamide metabolism homeostasis by driving cellular nicotinamide uptake [1,2]. It is associated with pathways related to energy metabolism, cellular respiration, and drug resistance [1,2]. Genetic models can be valuable in further exploring its functions.

In acute myeloid leukemia (AML), reduction of Slc29a1 expression decreased the cytotoxic effects of AraC, suggesting its contribution to the drug's efficacy [2]. In pancreatic cancer, activation of certain signaling pathways by ZIP4 led to the inhibition of ENT1 (encoded by Slc29a1), reducing gemcitabine uptake and increasing drug resistance [7]. In patients with chronic hepatitis C receiving telaprevir-based triple therapy, a polymorphism (rs760370) in the Slc29A1 gene influenced the severity of ribavirin-induced anaemia, possibly related to ribavirin uptake [3]. In hepatocellular carcinoma, low Slc29a1 expression was associated with poor prognosis, and its down-regulation enhanced tumor cell proliferation and invasion [5]. In brown adipose tissue, ENT1 (Slc29a1) regulated inosine levels, and its deficiency increased extracellular inosine, enhancing thermogenic adipocyte differentiation and counteracting diet-induced obesity [4]. In PC12 cells, miR-33-3p regulated cell proliferation and differentiation by targeting Slc29a1 [6].

In summary, Slc29a1 is essential for nucleoside and nicotinamide transport, impacting various biological processes. Studies using gene-based models have revealed its significance in multiple disease areas, including leukemia, pancreatic cancer, hepatitis C-related anaemia, hepatocellular carcinoma, obesity, and potentially neurological diseases, providing insights into disease mechanisms and potential therapeutic targets.

References:

1. Chen, Mingyang, Yuan, Luexiang, Chen, Binxin, Zhou, Hui, Jiang, Huidi. 2025. SLC29A1 and SLC29A2 are human nicotinamide cell membrane transporters. In Nature communications, 16, 1181. doi:10.1038/s41467-025-56402-y. https://pubmed.ncbi.nlm.nih.gov/39885119/

2. Kim, Jeong-Hyun, Lee, Chansu, Cheong, Hyun Sub, Shin, Hyoung Doo, Yoon, Sung-Soo. 2016. SLC29A1 (ENT1) polymorphisms and outcome of complete remission in acute myeloid leukemia. In Cancer chemotherapy and pharmacology, 78, 533-40. doi:10.1007/s00280-016-3103-x. https://pubmed.ncbi.nlm.nih.gov/27422302/

3. Milazzo, Laura, Peri, Anna Maria, Mazzali, Cristina, Antinori, Spinello, Falvella, Felicia Stefania. 2015. SLC29A1 polymorphism and prediction of anaemia severity in patients with chronic hepatitis C receiving triple therapy with telaprevir. In The Journal of antimicrobial chemotherapy, 70, 1155-60. doi:10.1093/jac/dku519. https://pubmed.ncbi.nlm.nih.gov/25583751/

4. Niemann, Birte, Haufs-Brusberg, Saskia, Puetz, Laura, Heeren, Joerg, Pfeifer, Alexander. 2022. Apoptotic brown adipocytes enhance energy expenditure via extracellular inosine. In Nature, 609, 361-368. doi:10.1038/s41586-022-05041-0. https://pubmed.ncbi.nlm.nih.gov/35790189/

5. Gao, Ping-Ting, Cheng, Jian-Wen, Gong, Zi-Jun, Fan, Jia, Yang, Xin-Rong. 2017. Low SLC29A1 expression is associated with poor prognosis in patients with hepatocellular carcinoma. In American journal of cancer research, 7, 2465-2477. doi:. https://pubmed.ncbi.nlm.nih.gov/29312800/

6. Shan, Bo-Quan, Li, Wen, He, Hui, Qin, Jian-Bing, Jin, Guo-Hua. 2021. miR-33-3p Regulates PC12 Cell Proliferation and Differentiation In Vitro by Targeting Slc29a1. In Neurochemical research, 46, 2403-2414. doi:10.1007/s11064-021-03377-z. https://pubmed.ncbi.nlm.nih.gov/34152551/

7. Liu, Mingyang, Zhang, Yuqing, Yang, Jingxuan, Houchen, Courtney W, Li, Min. 2019. ZIP4 Increases Expression of Transcription Factor ZEB1 to Promote Integrin α3β1 Signaling and Inhibit Expression of the Gemcitabine Transporter ENT1 in Pancreatic Cancer Cells. In Gastroenterology, 158, 679-692.e1. doi:10.1053/j.gastro.2019.10.038. https://pubmed.ncbi.nlm.nih.gov/31711924/