miR-26a-Targeting SLC7A11 Regulates Erastin-Induced Granulosa Cell Ferroptosis

TL;DR

This study shows that miR-26a promotes ferroptosis in granulosa cells by targeting SLC7A11, which could impact ovarian health and fertility.

Contribution

The novel finding is that miR-26a regulates granulosa cell ferroptosis by suppressing SLC7A11, offering a new perspective on ovarian function.

Findings

miR-26a expression is upregulated in erastin-treated oocytes.

Overexpression of miR-26a promotes ferroptosis in granulosa cells.

miR-26a reduces SLC7A11, impairing glutathione synthesis and antioxidant capacity.

Abstract

Granulosa cell ferroptosis is a critical factor in follicular atresia and premature ovarian insufficiency (POI). As a regulated form of programmed cell death, ferroptosis is gaining significant attention in reproductive medicine research. MicroRNAs (miRNAs) play a crucial role in regulating key aspects of ferroptosis, including the glutathione-GPX4 pathway, glutamate/cystine transport, and iron and lipid metabolism. The present study demonstrates that miR-26a positively modulates ferroptosis by targeting SLC7A11, a member of the solute carrier family. We found that oocytes and granulosa cells are susceptible to the ferroptosis inducer erastin, and employed RNA sequencing to delineate the miRNA expression profiles during erastin-induced damage and ferroptosis. Notably, miR-26a expression was significantly upregulated in erastin-treated oocytes. Importantly, overexpression of miR-26a promoted ferroptosis in granulosa cells, while its knockdown inhibited this process. Ectopic miR-26a expression suppressed SLC7A11, thereby increasing ferroptosis. Our findings indicate that miR-26a influences ferroptosis by inhibiting glutathione synthesis, reducing cellular antioxidant capacity, and suggesting a potential strategy to enhance reproductive potential.

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