The major miR‐31 target genes STK40 and LATS2 and their implications in the regulation of keratinocyte growth and hair differentiation

Abstract

Emerging evidence indicates that even subtle changes in the expression of key genes of signalling pathways can have profound effects. MicroRNAs (miRNAs) are masters of subtlety and generally have only mild effects on their target genes. The microRNA miR-31 is one of the major microRNAs in many cutaneous conditions associated with activated keratinocytes, such as the hyperproliferative diseases psoriasis, non-melanoma skin cancer and hair follicle growth. miR-31 is a marker of the hair growth phase, and in our miR-31 transgenic mouse model it impairs the function of keratinocytes. This leads to aberrant proliferation, apoptosis, and differentiation that results in altered hair growth, while the loss of miR-31 leads to increased hair growth. Through in vitro and in vivo studies, we have defined a set of conserved miR-31 target genes, including LATS2 and STK40, which serve as new players in the regulation of keratinocyte growth and hair follicle biology. LATS2 can regulate growth of keratinocytes and we have identified a function of STK40 that can promote the expression of key hair follicle programme regulators such as HR, DLX3 and HOXC13.

RNAseq-Based Prioritization Revealed COL6A5, COL8A1, COL10A1 and MIR146A as Common and Differential Susceptibility Biomarkers for Psoriasis and Psoriatic Arthritis: Confirmation from Genotyping Analysis of 1417 Italian Subjects

“…As previously discussed, KIF3A is involved in bone metabolism and has been associated with PsA, but not with Ps. The functions of STK40 are still unclear, although a role for this gene in the regulation of keratinocyte proliferation and hair follicle differentiation has been described [25]. Therefore, the presence of the risk allele (rs2910164 G) in the miRNA sequence may cause downstream deregulations that exacerbate the inflammatory context and influence the proliferation-related processes, contributing to the etiopathogenesis of Ps and PsA.…”

MicroRNA-31 Can Positively Regulate the Proliferation, Differentiation and Migration of Keratinocytes

“…Bcl-2, Bcl-XL and TAB1 Induces apoptosis and reverses the profibrotic phenotype in SSc dermal fibroblasts [26,27] miR-31 Psoriasis ppp6c, Pwp1 Enhances the proliferation of psoriasis keratinocytes [28,29] Skin wound Rasa1, Spred1, Spred2, SPRY4, EMP-1, LATS2 and STK40 Drives keratinocyte proliferation and migration to promote wound re-epithelialization [30][31][32] Melanoma SOX10 Suppresses cell growth and enhances the chemosensitivity of melanoma cells [33] miR-124 Skin wound SERP1 Inhibits keratinocyte proliferation, collagen biosynthesis [34] miR-126 Skin wound p-AKT, p-ERK2, and PI3 K Enhances viability, colony formation, and migration of keratinocytes HaCaT cells [35] miR-130a…”

Research progress on the relationship between zinc deficiency, related microRNAs, and esophageal carcinoma

“…STK40 is a negative regulator of nuclear factor kappa B (NF-κB)-mediated transcription and acts as a tumor suppressor directly targeted by miR-31. [36][37][38] Taccioli et al simulated the features of human EC using a rat model and examined the mechanism whereby Zn regulates miR-31 expression to promote EC progression. Zn deficiency induced the overexpression of miR-31 in a rat EC model.…”

“…In summary, miR‐223 is upregulated and is accompanied by the downregulation of its target tumor suppressor genes FBXW7, PARP1 , and SMARCD1 in EC. STK40 is a negative regulator of nuclear factor kappa B (NF‐κB)‐mediated transcription and acts as a tumor suppressor directly targeted by miR‐31 …”