Nova1, also known as Neuro-oncological ventral antigen 1, is a neuron-specific RNA-binding protein. It functions as a brain-specific splicing factor, regulating neuronal alternative splicing and playing a crucial role in neural development and function [4]. It is associated with pathways such as Wnt/β-catenin signaling in cancer-related processes [2]. Genetic models, like KO/CKO mouse models, are valuable for studying its functions.

In a conditional Nova1-null mouse (Nova1-cKOGad2-cre), loss of Nova1 in Gad2-positive neurons altered downstream expression of Impact mRNA and other related RNAs, revealing its role in hypothalamic function, translation, and metabolism [3]. In human glioblastoma cells, knockdown of NOVA1 disrupted cancer cell fitness, showing its oncogenic role in regulating cholesterol homeostasis [1]. In non-small cell lung cancer (NSCLC), siRNA-mediated down-regulation of NOVA1 inhibited cell proliferation, migration, and invasion, indicating its role in promoting NSCLC progression via the Wnt/β-catenin signaling pathway [2].

In conclusion, Nova1 is essential for neural development, hypothalamic function, and translation. Model-based research, especially KO/CKO mouse models, has revealed its significant roles in diseases such as glioblastoma and NSCLC. Understanding Nova1's functions provides insights into the mechanisms of these diseases and potential therapeutic targets.

References:

1. Saito, Yuhki, Yang, Yanhong, Saito, Misa, Tabar, Viviane, Darnell, Robert B. 2024. NOVA1 acts as an oncogenic RNA-binding protein to regulate cholesterol homeostasis in human glioblastoma cells. In Proceedings of the National Academy of Sciences of the United States of America, 121, e2314695121. doi:10.1073/pnas.2314695121. https://pubmed.ncbi.nlm.nih.gov/38416679/

2. Qu, Lianyue, Tian, Yulong, Wang, Fan, Li, Zixuan. 2022. NOVA1 promotes NSCLC proliferation and invasion by activating Wnt/β-catenin signaling. In BMC cancer, 22, 1091. doi:10.1186/s12885-022-10164-8. https://pubmed.ncbi.nlm.nih.gov/36284263/

3. Tajima, Yoko, Ito, Keiichi, Yuan, Yuan, Saito, Yuhki, Darnell, Robert B. 2023. NOVA1 acts on Impact to regulate hypothalamic function and translation in inhibitory neurons. In Cell reports, 42, 112050. doi:10.1016/j.celrep.2023.112050. https://pubmed.ncbi.nlm.nih.gov/36716149/

4. Xin, Yu, Li, Zheng, Zheng, Heyi, Chan, Matthew T V, Wu, William K K. 2017. Neuro-oncological ventral antigen 1 (NOVA1): Implications in neurological diseases and cancers. In Cell proliferation, 50, . doi:10.1111/cpr.12348. https://pubmed.ncbi.nlm.nih.gov/28394091/