Frontiers in Molecular Biosciences (Apr 2025)
Regulation of SLC7A11 by LncRNA GPRC5D-AS1 mediates ferroptosis in skeletal muscle: Mechanistic exploration of sarcopenia
Abstract
Sarcopenia is a chronic, progressive disease characterized by the gradual loss of skeletal muscle strength and mass. This study investigates the role of the long non-coding RNA GPRC5D-AS1 in the development and progression of sarcopenia through its regulation of SLC7A11. Skeletal muscle samples were obtained from sarcopenia patients and healthy controls to assess the expression levels of GPRC5D-AS1 and SLC7A11. Flow cytometry was used to evaluate iron content, lipid peroxidation, and antioxidant markers. A ferroptosis model was established in human skeletal muscle cells (HSKM) using the inducer erastin, and GPRC5D-AS1 overexpression plasmids were introduced to observe their effects on cell proliferation and ferroptosis indicators. In the sarcopenia group, both GPRC5D-AS1 and SLC7A11 expression levels decreased significantly, along with SLC7A11 protein translation. Erastin treatment markedly reduced cell viability and increased iron content, elevating ferroptosis marker genes (COX2, ACSL4, PTGS2, NOX1) while reducing GPX4 and FTH1 levels. The overexpression of GPRC5D-AS1 reversed these changes, enhancing antioxidant capacity and cell survival. Conversely, silencing SLC7A11 diminished the protective effects of GPRC5D-AS1 on cell proliferation and ferroptosis. These findings suggest that GPRC5D-AS1 overexpression increases SLC7A11 expression and reduces ferroptosis incidence in HSKM.
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