Downregulation of miR‐337‐3p in hypoxia/reoxygenation neuroblastoma cells increases KCTD11 expression

• Published in: Journal of biochemical and molecular toxicology 2024-04, Vol.38 (4), p.e23685-n/a
• Main Authors: Zhu, Lin, Xin, Yi‐Juan, He, Mu, Bian, Jun, Cheng, Xiao‐Li, Li, Rui, Li, Jin‐Jie, Wang, Juan, Liu, Jia‐Yun, Yang, Liu
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis; Cell death; Cell survival; Down-Regulation; Gene expression; Gene Expression Regulation; Gene regulation; Hypoxia; Hypoxia - metabolism; hypoxia/reoxygenation; KCTD11; Mice; MicroRNAs; MicroRNAs - genetics; MicroRNAs - metabolism; miRNA; miR‐337‐3p; Nerves; Neuroblastoma; Neuroblastoma - genetics; Neuroblasts; Neurodegeneration; Neuro‐2a; Physiological effects; Physiological responses; Regulatory mechanisms (biology); Ribonucleic acid; RNA; Side effects; Transcription activation; Transcription factors
• ISSN: 1095-6670; 1099-0461
• DOI: 10.1002/jbt.23685

Neurodegeneration is linked to the progressive loss of neural function and is associated with several diseases. Hypoxia is a hallmark in many of these diseases, and several therapies have been developed to treat this disease, including gene expression therapies that should be tightly controlled to avoid side effects. Cells experiencing hypoxia undergo a series of physiological responses that are induced by the activation of various transcription factors. Modulation of microRNA (miRNA) expression to alter transcriptional regulation has been demonstrated to be beneficial in treating multiple diseases, and in this study, we therefore explored potential miRNA candidates that could influence hypoxia‐induced nerve cell death. Our data suggest that in mouse neuroblasts Neuro‐2a cells with hypoxia/reoxygenation (H/R), miR‐337‐3p is downregulated to increase the expression of Potassium channel tetramerization domain containing 11 (KCTD11) and subsequently promote apoptosis. Here, we demonstrate for the first time that KCTD11 plays a role in the cellular response to hypoxia, and we also provide a possible regulatory mechanism by identifying the axis of miR‐337‐3p/KCTD11 as a promising candidate modulator of nerve cell survival after H/R exposure. Key points miR‐337‐3p is downregulated in hypoxia/reoxygenation exposed Neuro‐2a cells, and this downregulation then results in an increased expression of Potassium channel tetramerization domain containing 11 (KCTD11) that subsequently induces apoptosis. Cul‐3/E3 ubiquitin/hedgehog pathway is suggested to function as the possible signaling pathway of KCTD11 in hypoxia.