SH-SY5Y human neuronal cells with mutations of the CDKN2B-AS1 gene are vulnerable under cultured conditions
2024
Michiko Ohno-Oishi | Zou Meiai | Kota Sato | Seiya Kanno | Chihiro Kawano | Makoto Ishikawa | Toru Nakazawa
Glaucoma is a common cause of blindness worldwide. Genetic effects are believed to contribute to the onset and progress of glaucoma, but the underlying pathological mechanisms are not fully understood. Here, we set out to introduce mutations into the CDKN2B-AS1 gene, which is known as being the closely associated with glaucoma, in a human neuronal cell line in vitro. We introduced gene mutations with CRISPR/Cas9 into exons and introns into the CDKN2B-AS1 gene. Both mutations strongly promoted neuronal cell death in normal culture conditions. RNA sequencing and pathway analysis revealed that the transcriptional factor Fos is a target molecule regulating CDKN2B-AS1 overexpression. We demonstrated that gene mutation of CDKN2B-AS1 is directly associated with neuronal cell vulnerability in vitro. Additionally, Fos, which is a downstream signaling molecule of CDKN2B-AS1, may be a potential source of new therapeutic targets for neuronal degeneration in diseases such as glaucoma.
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