Neat1-KO Mouse

Neat1, also known as nuclear paraspeckle assembly transcript 1, is a long non-coding RNA. It is a vital component of paraspeckles, playing an essential role in their formation and integrity. Neat1 is involved in multiple biological pathways, including those related to cell cycle, proliferation, apoptosis, and migration. It has been linked to various diseases, highlighting its overall biological importance. Genetic models, such as KO/CKO mouse models, are valuable for studying Neat1's functions [2,3,4].

In hepatocellular carcinoma (HCC), Neat1 deficiency caused senescence in cultured hepatoma cells and protected against HCC progression in a mouse model. This was associated with KIF11-dependent repression of CDKN2A, suggesting Neat1 overexpression reduces senescence and promotes tumor progression in HCC [1].

In stroke-related research, knockdown of Neat1 in a preclinical stroke mouse model significantly alleviated lipid droplet agglomeration and inhibited autophagy in microglia, leading to improved cerebral perfusion, reduced brain injury, and increased neurological recovery, indicating Neat1 is a key player in lipid droplet agglomeration and autophagy stimulation post-stroke [5].

In conclusion, Neat1 is crucial for the integrity of paraspeckles and is involved in multiple biological processes. Model-based research, especially through Neat1 KO/CKO mouse models, has revealed its role in diseases like HCC and stroke. Understanding Neat1 provides insights into disease mechanisms and potential therapeutic targets for these conditions.

References:

1. Chen, Danlei, Wang, Jinghao, Li, Yang, Zhang, Pengfei, Liu, Lianxin. . LncRNA NEAT1 suppresses cellular senescence in hepatocellular carcinoma via KIF11-dependent repression of CDKN2A. In Clinical and translational medicine, 13, e1418. doi:10.1002/ctm2.1418. https://pubmed.ncbi.nlm.nih.gov/37752791/

2. Saleh, Raed Obaid, Alkhafaji, Adnan Taan, Mohammed, Jaafaru Sani, Jawad, Mohammed Abed, Zwamel, Ahmed Hussein. . LncRNA NEAT1 in the pathogenesis of liver-related diseases. In Cell biochemistry and function, 42, e4006. doi:10.1002/cbf.4006. https://pubmed.ncbi.nlm.nih.gov/38622913/

3. Pisani, Gabriel, Baron, Byron. 2020. NEAT1 and Paraspeckles in Cancer Development and Chemoresistance. In Non-coding RNA, 6, . doi:10.3390/ncrna6040043. https://pubmed.ncbi.nlm.nih.gov/33143162/

4. Bu, Fang-Tian, Wang, Ao, Zhu, Yan, Huang, Cheng, Li, Jun. 2020. LncRNA NEAT1: Shedding light on mechanisms and opportunities in liver diseases. In Liver international : official journal of the International Association for the Study of the Liver, 40, 2612-2626. doi:10.1111/liv.14629. https://pubmed.ncbi.nlm.nih.gov/32745314/

5. Pan, Yongli, Xin, Wenqiang, Wei, Wei, Huttner, Hagen B, Doeppner, Thorsten R. 2024. Knockdown of NEAT1 prevents post-stroke lipid droplet agglomeration in microglia by regulating autophagy. In Cellular and molecular life sciences : CMLS, 81, 30. doi:10.1007/s00018-023-05045-7. https://pubmed.ncbi.nlm.nih.gov/38212456/