Photo Credit: Zay Nyi Nyi

The following is a summary of “N6-methyladenosine modification of lnc-CCKAR-5 regulates autophagy in human umbilical cord mesenchymal stem cells by destabilizing LMNA and inhibits diabetic wound healing,” published in the January 2024 issue of Dermatology by Wang et al.

Long noncoding RNAs (lncRNAs) emerge as crucial players in the pathogenesis of various human diseases, yet their specific implications in diabetic wound healing mediated by human umbilical cord mesenchymal stem cells (hUCMSCs) remain elusive. 

This study elucidates the role of lncCCKAR5 in this context. Their investigation reveals a significant downregulation of lncCCKAR5 expression in hUCMSCs under high glucose conditions, with consequential effects on autophagy modulation and apoptosis inhibition. Notably, the diminished expression of lncCCKAR5 effectively impedes cellular senescence and fosters filopodium formation. Mechanistically, lncCCKAR5 serves as a scaffold, facilitating the interaction between MKRN2 and LMNA, a key regulator of cytoskeletal function and autophagy. 

The resulting LncCCKAR5/LMNA/MKRN2 complex plays a pivotal role in promoting ubiquitin-mediated degradation of LMNA, with N6-adenosine methylation of LncCCKAR5 further enhancing this effect. Their comprehensive findings underscore the critical regulatory role of LncCCKAR5 in the autophagic process within hUCMSCs, particularly through the intricate interplay of protein ubiquitination and degradation. This complex regulatory network unveils a promising avenue for potential therapeutic interventions in diabetic wound healing involving hUCMSCs.

Source: sciencedirect.com/science/article/abs/pii/S0022202X23032165