CircRNA FUT10 regulates the regenerative potential of aged skeletal muscle stem cells by targeting HOXA9

Abstract

Skeletal muscle is capable of repairing itself after injury to maintain the stability of its own tissue, but this ability declines with aging. Circular RNAs (circRNAs) are involved in cell aging. However, there is little research into their role and underlying mechanisms, especially in skeletal muscle stem cells (SkMSCs). In this study, we assessed circRNA FUT10 expression in aged and adult SkMSCs. We observed that circRNA FUT10 was upregulated in aged SkMSCs compared with that in adult SkMSCs. Furthermore, we identified putative miR-365-3p binding sites on circRNA FUT10, suggesting that this circRNA sponges miR-365a-3p. We also found that HOXA9 is a downstream target of miR-365a-3p and confirmed that miR-365a-3p can bind to circRNA FUT10 and the 3′-untranslated region of HOXA9 mRNA. This finding indicated that miR-365a-3p might serve as a “bridge” between circRNA FUT10 and HOXA9. Finally, we found that the circRNA FUT10/miR365a-3p/HOXA9 axis is involved in SkMSC aging. Collectively, our results show that the circRNA FUT10/miR365a-3p/HOXA9 axis is a promising therapeutic target and are expected to facilitate the development of therapeutic strategies to improve the prognosis of degenerative muscle disease.

CircRNAs Related to Breast Muscle Development and Their Interaction Regulatory Network in Gushi Chicken

“…MiR-499-5p can regulate the development of skeletal muscle by regulating muscle gene expression through the NFATc1/MEF2C pathway [ 46 ]. In addition, studies have found that circRNA FUT10 can act as a sponge for miR-365a-3p to regulate the expression of HOXA9 and then regulate the senescence of skeletal muscle stem cells [ 47 ]; a novel circular RNA produced by FGFR2 gene by sponge miR-133a-5p and miR-29b-1-5p promotes myoblast proliferation and differentiation [ 12 ]; circMYBPC1 can promote myoblast differentiation by targeting MyHC and may promote skeletal muscle regeneration [ 48 ]. These findings suggest that circRNAs may play an intrinsic competition-regulated role during skeletal muscle development by interacting with miRNA.…”

Comprehensive Analysis of Differentially Expressed mRNAs, lncRNAs and circRNAs Related to Intramuscular Fat Deposition in Laiwu Pigs

“…Further studies using new methods would be required to reveal the regulation mechanism of IMF deposition. In recent years, advances in sequencing technology have revealed that long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs) have emerged as important class of gene expression regulators that can regulate numerous biological processes, such as cancer progression, neurological disorders, cancer cell proliferation, and muscle contraction [ 4 , 5 , 6 , 7 , 8 , 9 , 10 ]. Studies had proven that several lncRNAs and circRNAs are involved in adipogenesis.…”

The emerging roles of circRNAs in traits associated with livestock breeding

“…The most significantly different circRNA was found to be circFUT10. The circFUT10 inhibited the differentiation of adult skeletal muscle stem cells by reducing the expression of MyoD and MyHC, while inhibition of circFUT10 promoted the differentiation of skeletal muscle stem cells in the aged group (Zhu et al, 2021). During myogenesis, circNfix acted as a sponge for miR‐204 to enhance MEF2C expression and promote myotube formation (Das et al, 2021).…”