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bioRxiv · 10.1101/2023.04.04.535506

p53 translational isoform {triangleup}40p53 orchestrates cellular SGSH levels via microRNA-4671-5p to modulate cell cycle

PAL, A.·Khan, D.·Tripathi, S. K.·Ghosh, P. K.·Ghosh, S.·Patra, S.·Maitra, A.·Das, S.
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Abstract

{Delta}40p53, the only translational isoform of p53, modulates the full-length p53 (FLp53) activity and independently regulates targets such as the miR-186-5p-YY1 axis. To identify additional miRNAs regulated by {Delta}40p53, we performed small RNA sequencing. We found that overexpression of {Delta}40p53, but not FLp53, significantly downregulated miR-4671-5p. Expression of both isoforms at varying ratios revealed that miR-4671-5p may be modulated by FLp53 in a {Delta}40p53-dependent manner. In silico analysis identified SGSH (N-sulfoglucosamine sulfohydrolase) as a potential miR-4671-5p target. SGSH expression showed inverse correlation with miR-4671-5p in cancer datasets and prognostic significance. SGSH mRNA and protein levels were reduced upon miR-4671-5p overexpression or si{Delta}40p53 treatment, confirming regulatory linkage. Functionally, miR-4671-5p overexpression induced intra-S-phase cell cycle arrest, implicating SGSH in cell cycle regulation. These results reveal a novel {Delta}40p53-miR-4671-5p-SGSH axis that impacts cell cycle progression and may contribute to cancer outcomes. Our findings highlight the distinct regulatory role of {Delta}40p53, independent of FLp53, in maintaining cellular and metabolic homeostasis via miRNA-mediated mechanisms.

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PAL, A., Khan, D., Tripathi, S. K., Ghosh, P. K., Ghosh, S., Patra, S., Maitra, A., Das, S.. 2023-04-04. p53 translational isoform {triangleup}40p53 orchestrates cellular SGSH levels via microRNA-4671-5p to modulate cell cycle. https://doi.org/10.1101/2023.04.04.535506

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