Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

miR‐27a‐3p via FTO is Involved in Arsenit‐Induced Apoptosis of HT22 Cells

Version 1 : Received: 28 April 2024 / Approved: 29 April 2024 / Online: 29 April 2024 (16:44:41 CEST)

How to cite: Zhang, Q.; Ma, T.; Wang, Y.; Xu, S.; Zhao, S.; Wang, S.; Wang, X.; Wang, L. miR‐27a‐3p via FTO is Involved in Arsenit‐Induced Apoptosis of HT22 Cells. Preprints 2024, 2024041935. https://doi.org/10.20944/preprints202404.1935.v1 Zhang, Q.; Ma, T.; Wang, Y.; Xu, S.; Zhao, S.; Wang, S.; Wang, X.; Wang, L. miR‐27a‐3p via FTO is Involved in Arsenit‐Induced Apoptosis of HT22 Cells. Preprints 2024, 2024041935. https://doi.org/10.20944/preprints202404.1935.v1

Abstract

Environmental arsenic exposure is closely related to nerve damage, and chronic arsenic exposure will cause neurotoxicity and damage the nervous system. Recent research suggests miR-27a-3p is required for the progression of certain neurodegenerative and neuropsychiatric disorders. Nonetheless, the precise impact of miR-27a-3p on neuron functioning in the hippocampus remains unclear. In this investigation, models were established using arsenite-treated cells and mice to investigate this aspect. After male C57BL/6J mice were exposed to arsenite (0, 0.5, 5 or 50ppm) in drinking water for 48 weeks, Nissl staining, terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) assay, and Hematoxylin-Eosin (H&E) stainingrevealed an arsenite-induced neuronal injury and apoptosis. For 6 μmol/L arsenite-treated HT22 cells, arsenite decreases miR-27a-3p levels and activated the FTO/DRP1 pathway. For arsenite-treated HT222 cells, the increases of FTO and DRP1 and p-DRP1 (Ser616) levels induced by arsenite were reversed by miR-27a-3p mimic.Furthermore, the increases of neuronal apoptosis and pro-apoptotic protein (Bax and Cleaved-caspase 3) levels as well as decreased levels of anti-apoptotic proteins Bcl-2 induced by arsenite were reversed by miR-27a-3p mimic in HT22 cells. Moreover,the decreases of MMP induced by arsenitewas reversed by miR-27a-3p mimic. Overall, in HT22 cells exposed to arsenite, miR-27a-3p mitigates neuronal apoptosis, suggesting its potential utility in addressing arsenite accumulation and associated with brain pathologies. Dysregulated expression patterns of miRNAs in the hippocampus have emerged as pivotal elements in neuronal apoptosis linked to neurological dysfunction, with miR-27a-3p specifically implicated in apoptotic pathways.

Keywords

miR-27a-3p; Arsenic; Apoptosis; Hippocampal

Subject

Public Health and Healthcare, Public, Environmental and Occupational Health

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