Snhg8-KO Mouse

Snhg8, or small nucleolar RNA host gene 8, is a long non-coding RNA. It has physiological roles in epithelial and muscle satellite cells and is involved in various biological processes. It can act as a molecular sponge for multiple miRNAs, regulating their target genes, and is associated with pathways such as the NF-κB signaling pathway [1].

In tauopathies, Snhg8 was significantly reduced in a mouse model and in human brains with FTLD-tau, progressive supranuclear palsy, and Alzheimer's disease. Overexpression of mutant tau reduces Snhg8 expression and induces stress granule formation, while rescuing Snhg8 expression leads to reduced stress granule formation, suggesting its role in driving stress granule formation via TIA1 in tauopathies [2]. In many cancer types like EBV-associated gastric cancer, breast cancer, nasopharyngeal carcinoma, and diffuse large B-cell lymphoma, Snhg8 acts as an oncogene. For example, in EBV-associated gastric cancer, it promotes tumorigenesis and invasion by sponging miR-512-5p and upregulating TRIM28 [3]. In contrast, in osteogenic differentiation of periodontal ligament stem cells, mechanical force reduces Snhg8 expression, which promotes osteogenic differentiation, and knockdown of Snhg8 increases the expression of osteogenic-related genes [4]. Also, in cerebral ischemia-reperfusion injury, overexpression of Snhg8 in microglial cells inhibits the inflammatory reaction and apoptosis by inhibiting miR-494-3p expression [5].

In summary, Snhg8 has diverse functions. In disease models, it is closely associated with neurodegenerative diseases like tauopathies and various cancers, where its dysregulation impacts key cellular processes. Understanding Snhg8 through these models helps to clarify its role in disease mechanisms, potentially offering new therapeutic targets for related diseases.

References:

1. Ghafouri-Fard, Soudeh, Harsij, Atefeh, Hussen, Bashdar Mahmud, Taheri, Mohammad, Ayatollahi, Seyed Abdulmajid. 2023. A review on the role of SNHG8 in human disorders. In Pathology, research and practice, 245, 154458. doi:10.1016/j.prp.2023.154458. https://pubmed.ncbi.nlm.nih.gov/37043963/

2. Bhagat, Reshma, Minaya, Miguel A, Renganathan, Arun, Grinberg, Lea T, Karch, Celeste M. 2023. Long non-coding RNA SNHG8 drives stress granule formation in tauopathies. In Molecular psychiatry, 28, 4889-4901. doi:10.1038/s41380-023-02237-2. https://pubmed.ncbi.nlm.nih.gov/37730840/

3. Zou, Changyan, Liao, Jinrong, Hu, Dan, Huang, Tao, Lin, Xiandong. 2021. SNHG8 Promotes the Progression of Epstein-Barr Virus-Associated Gastric Cancer via Sponging miR-512-5p and Targeting TRIM28. In Frontiers in oncology, 11, 734694. doi:10.3389/fonc.2021.734694. https://pubmed.ncbi.nlm.nih.gov/34722282/

4. Zhang, Zijie, He, Qin, Yang, Shuangyan, Li, Xiaoyu, Wei, Fulan. 2022. Mechanical force-sensitive lncRNA SNHG8 inhibits osteogenic differentiation by regulating EZH2 in hPDLSCs. In Cellular signalling, 93, 110285. doi:10.1016/j.cellsig.2022.110285. https://pubmed.ncbi.nlm.nih.gov/35192931/

5. Cao, T, Liu, Q, Pan, M, Zhang, X. . [LncRNA SNHG8 inhibits miR-494-3p expression to alleviate cerebral ischemia-reperfusion injury in mice]. In Nan fang yi ke da xue xue bao = Journal of Southern Medical University, 43, 2015-2022. doi:10.12122/j.issn.1673-4254.2023.12.04. https://pubmed.ncbi.nlm.nih.gov/38189386/