N4bp2l1, also known as NEDD4 binding protein 2-like 1, has diverse functions. It is involved in adipocyte homeostasis, with implications for glucose uptake and the insulin signaling pathway through its interaction with dynein-dynactin, contributing to GLUT4 trafficking in adipocytes [1]. It may also play a role in muscle cell development and has potential tumor-suppressive functions in breast cancer, as its expression is downregulated in breast tumors [2].

In adipocyte-related studies, N4bp2l1 expression increases in 3T3-L1 cells during differentiation. Knockdown of N4bp2l1 suppresses adipocyte differentiation, indicating its importance in adipogenesis. It is a novel FoxO1 and USF1 target gene, with its expression controlled by insulin-mediated regulation of FoxO1 and USF1 directly binding to its promoter [1,3]. In cancer-related research, in oral squamous cell carcinoma, knockdown of N4bp2l1 reduces the invasive potential of cancer cells, and its overexpression is associated with nodal metastasis and poor prognosis [4]. In bladder cancer, miR-150-5p targets N4bp2l1, and N4bp2l1 knockdown mimics the inhibitory effects of miR-150-5p on cell proliferation, migration, and invasion [5].

In conclusion, N4bp2l1 is crucial for adipocyte differentiation, glucose metabolism, and may have tumor-related functions. Studies using knockdown models in adipocytes and cancer cells have revealed its role in these biological processes and disease conditions, providing insights into potential therapeutic targets for metabolic and cancer-related diseases.

References:

1. Watanabe, Kazuhisa, Matsumoto, Ayumi, Tsuda, Hidetoshi, Iwamoto, Sadahiko. 2021. N4BP2L1 interacts with dynactin and contributes to GLUT4 trafficking and glucose uptake in adipocytes. In Journal of diabetes investigation, 12, 1958-1966. doi:10.1111/jdi.13623. https://pubmed.ncbi.nlm.nih.gov/34197691/

2. Dastsooz, Hassan, Anselmi, Francesca, Lauria, Andrea, Caizzi, Livia, Oliviero, Salvatore. 2024. Involvement of N4BP2L1, PLEKHA4, and BEGAIN genes in breast cancer and muscle cell development. In Frontiers in cell and developmental biology, 12, 1295403. doi:10.3389/fcell.2024.1295403. https://pubmed.ncbi.nlm.nih.gov/38859961/

3. Watanabe, Kazuhisa, Yokota, Kazuha, Yoshida, Ken, Matsumoto, Ayumi, Iwamoto, Sadahiko. 2019. A novel upstream transcription factor 1 target gene N4bp2l1 that regulates adipogenesis. In Biochemistry and biophysics reports, 20, 100676. doi:10.1016/j.bbrep.2019.100676. https://pubmed.ncbi.nlm.nih.gov/31440585/

4. Sasahira, Tomonori, Kurihara, Miyako, Nishiguchi, Yukiko, Kirita, Tadaaki, Kuniyasu, Hiroki. 2016. NEDD 4 binding protein 2-like 1 promotes cancer cell invasion in oral squamous cell carcinoma. In Virchows Archiv : an international journal of pathology, 469, 163-72. doi:10.1007/s00428-016-1955-4. https://pubmed.ncbi.nlm.nih.gov/27184799/

5. Rao, Pinlang, Li, Jianmin, Xiong, Junhui, Zeng, Jingwen, Zhao, Hong. 2024. MicroRNA-150-5p-mediated Inhibition of Cell Proliferation, G1/S Transition, and Migration in Bladder Cancer through Targeting NEDD4-binding Protein 2-like 1 Gene. In Journal of physiological investigation, 67, 118-128. doi:10.4103/ejpi.EJPI-D-24-00009. https://pubmed.ncbi.nlm.nih.gov/38910572/