MicroRNAs-103/107 Regulate Autophagy in the Epidermis

Abstract

We have shown that microRNAs-103 and -107 (miRs-103/107) positively regulate end-stage autophagy by ensuring dynamin activity in cultured keratinocytes. Most work in end-stage autophagy has been conducted using in vitro model systems. In vivo regulation of end-stage autophagy in epidermis remains unknown. Here, we used antagomirs to subcutaneously knock down miR-107 in the skin; conversely, we delivered miR-107 mimic subcutaneously via in vivo transfection to increase this miR. We found that antagomir-107 treatment in epidermis: (i) depleted endogenous miR-107; (ii) increased GFP-LC3 puncta in epidermal basal layers of GFP-LC3 transgenic mice, indicative of an accumulation of autophagosomes; (iii) inhibited LC3 turnover and increased p62, suggesting an inhibition of autophagy flux; and (iv) increased phosphorylated dynamin (p-dynamin, an inactive form), a key enzyme in end-stage autophagy. Conversely, miR-107 mimic treatment in mouse epidermis: decreased GFP-LC3 puncta in basal layer, as well as p62 protein levels; and diminished p-dynamin, indicative of activation of this enzyme. In human epidermal keratinocytes, antagos-103/107 cause the formation of large vacuoles and an increase in p-dynamin, which can be rescued by inhibition of protein kinase C pathway. Collectively, these results suggest that the miR-103/107 family has a critical role in regulating end-stage autophagy in mouse epidermis via PLD1/2-protein kinase C-dynamin pathway.

HMGA1 Induction of miR-103/107 Forms a Negative Feedback Loop to Regulate Autophagy in MPTP Model of Parkinson’s Disease

“…Furthermore, the specific role of miR-103/107 family during the progression of PD is still unclear. Previous studies have shown the important role of miR-103/107 family in regulating autophagy, especially end-stage autophagy, mediated by CDK5R1/CDK5 signaling pathway (Wang et al, 2018 , 2020 ). In addition, CDK5 has been demonstrated to induce MPTP-induced neuronal death by regulating autophagy (Wong et al, 2011 ) and survival factor MEF2, antioxidant enzyme Prx2, and DNA damage repair enzyme Ape1 (Cheung and Ip, 2012 ).…”

miR-874 regulates multiple-drug resistance in gastric cancer by targeting ATG16L1

“…miRNAs serve an important role in regulating autophagy (32,33). The expression of miR-874 was modified Table I.…”

Discovery of microRNA expression profiles involved in regulating TGF-β2 expression in the tears of dry eye patients

“…They also found that miR-103/107 can simultaneously regulate the following two important processes, which can not only ensure that the autophagy process persists to the final stage of cell division but also prevent excessive fluid intake from outside the cell during the giant cell drinking process. 10 However, the difference in miR expression profiles in tears of dry eye patients and healthy people has not been reported.…”

“…Wang et al. 10 pointed out that the miR-103/107 family plays an important role in regulating the biological processes of stem cells in the corneal limbal epithelial cells. They also found that miR-103/107 can simultaneously regulate the following two important processes, which can not only ensure that the autophagy process persists to the final stage of cell division but also prevent excessive fluid intake from outside the cell during the giant cell drinking process.…”