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bioRxiv · 10.1101/2025.10.06.680678

In Vitro Modulation of MECP2 Expression via Antisense Inhibition of miR-132-3p in SH-SY5Y Cells

Orcen, A.·Goncu, B.·Ekici, B.·Tatli, B.·Yucesan, E.
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Abstract

Rett syndrome (RTT) is a severe neurodevelopmental disorder that predominantly affects females. It is characterized by developmental regression during infancy, including loss of speech, gait abnormalities, intellectual disability, seizures, respiratory issues, and stereotypic hand movements. RTT is mainly caused by spontaneous, non-inherited mutations in the methyl-CpG-binding protein 2 (MECP2) gene located on the X chromosome. Despite considerable scientific progress, no effective treatments currently exist for MECP2-related pathology. Antisense oligonucleotides (ASOs), which selectively bind and inhibit specific RNA targets, have recently emerged as promising therapeutic agents. This study investigated the effects of ASO-mediated inhibition of miR132-3p on MECP2 mRNA expression in the SH-SY5Y neuroblastoma cell line to evaluate its therapeutic potential in RTT. Our results demonstrated a significant reduction in miR132-3p expression 6 hours after transfection with Mixmer and 2OMe-modified ASOs. Correspondingly, MECP2 mRNA levels were significantly upregulated in all ASO-treated groups, with the most prominent increase observed at 12 hours post-transfection in the 2OMe group. This time-dependent inverse relationship between miR132-3p and MECP2 expression supports the regulatory interaction between them. These findings suggest that 2OMe-modified ASOs targeting miR132-3p may represent a promising therapeutic strategy for RTT and warrant further in vivo investigation.

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Orcen, A., Goncu, B., Ekici, B., Tatli, B., Yucesan, E.. 2025-10-06. In Vitro Modulation of MECP2 Expression via Antisense Inhibition of miR-132-3p in SH-SY5Y Cells. https://doi.org/10.1101/2025.10.06.680678

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