An integrative analysis of the lncRNA-miRNA-mRNA competitive endogenous RNA network reveals potential mechanisms in the murine hair follicle cycle

Abstract

Alopecia is a common progressive disorder associated with abnormalities of the hair follicle cycle. Hair follicles undergo cyclic phases of hair growth (anagen), regression (catagen), and rest (telogen), which are precisely regulated by various mechanisms. However, the specific mechanism associated with hair follicle cycling, which includes noncoding RNAs and regulation of competitive endogenous RNA (ceRNA) network, is still unclear. We obtained data from publicly available databases and performed real-time quantitative polymerase chain reaction validations. These analyses revealed an increase in the expression of miRNAs and a decrease in the expression of target mRNAs and lncRNAs from the anagen to telogen phase of the murine hair follicle cycle. Subsequently, we constructed the ceRNA networks and investigated their functions using enrichment analysis. Furthermore, the androgenetic alopecia (AGA) microarray data analysis revealed that several novel alopecia-related genes were identified in the ceRNA networks. Lastly, GSPT1 expression was detected using immunohistochemistry. Our analysis revealed 11 miRNAs (miR-148a-3p, miR-146a-5p, miR-200a-3p, miR-30e-5p, miR-30a-5p, miR-27a-3p, miR-143-3p, miR-27b-3p, miR-126a-3p, miR-378a-3p, and miR-22-3p), 9 target mRNAs (Atp6v1a, Cdkn1a, Gadd45a, Gspt1, Mafb, Mitf, Notch1, Plk2, and Slc7a5), and 2 target lncRNAs (Neat1 and Tug1) were differentially expressed in hair follicle cycling. The ceRNA networks were made of 12 interactive miRNA-mRNA pairs and 13 miRNA-lncRNA pairs. The functional enrichment analysis revealed the enrichment of hair growth–related signaling pathways. Additionally, GSPT1 was downregulated in androgenetic alopecia patients, possibly associated with alopecia progression. The ceRNA network identified by our analysis could be involved in regulating the hair follicle cycle.

Role of HFSCARC in hair follicle stem cell proliferation and differentiation in cashmere goat

“…The HF cycle is a tightly regulated process, and emerging evidence suggests that lncRNAs play an essential role in its regulation [11, 15, 16]. We observed that HFSCARC expression was higher during the anagen phase of HF cycle compared to the telogen phase.…”

“…Long noncoding RNAs (lncRNAs) transcript are more than 200 nucleotides and do not encode proteins. Multiple lines of evidences showed that lncRNAs have been demonstrated to involve in HF cycle [11,12]. LncRNAs play multiple roles, including transcription regulation, chromatin remodeling, mRNA splicing, and editing, and involvement in proliferation, differentiation, apoptosis and other biological processes of HFSC [13,14].…”

Integrative analysis of Iso-Seq and RNA-seq data reveals transcriptome complexity and differential isoform in skin tissues of different hair length Yak

“…MiR-149-5p could induce hair follicle stem cell differentiation in goats by promoting the expression of β-catenin [30]. In addition, many studies also revealed the regulation relationship of miRNA-lncRNA-mRNA in hair follicle development [31][32][33]. APA is a kind of posttranscriptional process that could change the binding site of miRNA and mRNA [34].…”

Autophagy Dysfunction: The Kernel of Hair Loss?

“…Autophagy emerged as one of the augmented signaling pathways in a Kyoto Encyclopaedia of Genes and Genomes (KEGG) analysis of 105 downregulated mRNAs transitioning from the anagen to the catagen phase. 65 Additionally, a comprehensive evaluation of autophagic activity in the HF cycle on mice's dorsal skin revealed an elevation of autophagy in anagen, a diminution in catagen, and stable low levels during telogen. 66 Active autophagic flux was predominantly observed in hair matrix keratinocytes and dermal adipocytes encircling the HFs.…”