The Rejuvenation and Functional Restoration of Aged Adipose Stem Cells by DUXAP10 Knockdown via the Regulation of the miR-214-3p/RASSF5 Axis

Abstract

Abstract Adipose stem cell (ASC)-based therapies provide an encouraging option for tissue repair and regeneration. However, the function of these cells declines with aging, which limits their clinical transformation. Recent studies have outlined the involvement of long non-coding RNAs in stem cell aging. Here, we reanalyzed our published RNA sequencing (RNA-seq) data profiling differences between ASCs from young and old donors and identified a lncRNA named double homeobox A pseudogene 10 (DUXAP10) as significantly accumulated in aged ASCs. Knocking down DUXAP10 promoted stem cell proliferation and migration and halted cell senescence and the secretion of proinflammatory cytokines. In addition, DUXAP10 was located in the cytoplasm and functioned as a decoy for miR-214-3p. miR-214-3p was downregulated in aged ASCs, and its overexpression rejuvenated aged ASCs and reversed the harm caused by DUXAP10. Furthermore, Ras Association Domain Family Member 5 (RASSF5) was the target of miR-214-3p and was upregulated in aged ASCs. Overexpressing DUXAP10 and inhibiting miR-214-3p both enhanced RASSF5 content in ASCs, while DUXAP10 knockdown promoted the therapeutic ability of aged ASCs for skin wound healing. Overall, this study offers new insights into the mechanism of age-related ASC dysfunction and names DUXAP10 and miR-214-3p as potential targets for energizing aged stem cells.