Perspectives on miRNAs Targeting DKK1 for Developing Hair Regeneration Therapy

Abstract

Androgenetic alopecia (AGA) remains an unsolved problem for the well-being of humankind, although multiple important involvements in hair growth have been discovered. Up until now, there is no ideal therapy in clinical practice in terms of efficacy and safety. Ultimately, there is a strong need for developing a feasible remedy for preventing and treating AGA. The Wnt/β-catenin signaling pathway is critical in hair restoration. Thus, AGA treatment via modulating this pathway is rational, although challenging. Dickkopf-related protein 1 (DKK1) is distinctly identified as an inhibitor of canonical Wnt/β-catenin signaling. Thus, in order to stimulate the Wnt/β-catenin signaling pathway, inhibition of DKK1 is greatly demanding. Studying DKK1-targeting microRNAs (miRNAs) involved in the Wnt/β-catenin signaling pathway may lay the groundwork for the promotion of hair growth. Bearing in mind that DKK1 inhibition in the balding scalp of AGA certainly makes sense, this review sheds light on the perspectives of miRNA-mediated hair growth for treating AGA via regulating DKK1 and, eventually, modulating Wnt/β-catenin signaling. Consequently, certain miRNAs regulating the Wnt/β-catenin signaling pathway via DKK1 inhibition might represent attractive candidates for further studies focusing on promoting hair growth and AGA therapy.

Gender-Difference in Hair Length as Revealed by Crispr-Based Production of Long-Haired Mice with Dysfunctional FGF5 Mutations

“…Wnt/β-catenin signaling pathway plays an important role in regulating hair growth and entry into the anagen phase [ 38 , 39 , 40 ]. Dickkopf-related protein 1 (DKK1), a natural inhibitor of Wnt, strongly suppresses the Wnt/β-catenin signaling pathway [ 40 ].…”

“…Wnt/β-catenin signaling pathway plays an important role in regulating hair growth and entry into the anagen phase [ 38 , 39 , 40 ]. Dickkopf-related protein 1 (DKK1), a natural inhibitor of Wnt, strongly suppresses the Wnt/β-catenin signaling pathway [ 40 ]. Zhang et al [ 9 ] showed that the transcript levels of 5α-reductase type 1 ( SRD5A ), AR , and DKK1 were greatly reduced in Fgf5 KO sheep, suggesting a close relationship between FGF5 signaling and AR activation.…”

Potential utility of miRNAs for liquid biopsy in breast cancer

“…Argonaute (AGO) protein family recognizes miRNA and leads to the loading of miRNA guide strand into the RNA-induced silencing complex (RISC). The passenger strand is degraded and approximately 22 nucleotide-length miRNA containing seed region is ready to bind the specific region of the target messenger RNA (mRNA) molecule on the 3’untranslated region (3’UTR) that consequently leads to the silencing of the target gene ( 22 , 28 ). Remarkably, miRNAs are implicated in the regulation of key pathways that are usually genetically altered in various cancers.…”

“…Currently, over 3000 miRNAs are found in almost all human body fluids. These miRNAs are implicated in various processes and play a significant role in the progression or regression of a number of diseases (22)(23)(24)(25)(26). miRNAs vary in their function as they have a strong capacity of regulating multiple gene expression.…”

The Enticing Path of miR Therapeutics: Difficult but Not without Prospects

“…The DKK1 and Wnt/β-catenin regulation are critical approaches in promoting hair growth. Papukashvili et al reviewed the miRs (e.g., miR-103/107, miR-203, and miR-218) that could modulate the Wnt/β-catenin signaling pathway via regulating DKK1 and represent attractive therapeutic candidates [9]. Recent studies have shown the role of miRs in the pathogenesis of inflammatory bowel disease.…”