An integrative analysis of the lncRNA-miRNA-mRNA competitive endogenous RNA network reveals potential mechanisms in the murine hair follicle cycle.
An integrative analysis of the lncRNA-miRNA-mRNA competitive endogenous RNA network reveals potential mechanisms in the murine hair follicle cycle.
复制标题
对 lncRNA-miRNA-mRNA 竞争性内源 RNA 网络的综合分析揭示了小鼠毛囊周期的潜在机制。
DOI：
10.3389/fgene.2022.931797
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发表时间：
2022
影响因子：
3.7
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中科院分区：
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脱发是一种与毛囊周期异常相关的常见进行性疾病。毛囊经历毛发生长（生长期）、退化（退化期）和休止期（休止期）的周期性阶段，这些阶段由各种机制精确调节。然而，与毛囊周期相关的具体机制，包括非编码RNA和竞争性内源性RNA（ceRNA）网络的调控，仍然不清楚。我们从公开的数据库中获得数据，并进行实时定量聚合酶链反应验证。这些分析揭示了从小鼠毛囊周期的生长期到休止期，miRNA的表达增加，而靶mRNA和lncRNA的表达减少。随后，我们构建了ceRNA网络，并使用富集分析研究了它们的功能。此外，雄激素性脱发（阿加）芯片数据分析显示，几个新的脱发相关基因的ceRNA网络中确定。最后用免疫组化法检测GSPT 1的表达。我们的分析揭示了11个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和miR-22-3p），9种靶mRNA（Atp 6v 1a、Cdkn 1a、Gadd 45 a、Gspt 1、Mafb、Mitf、Notch 1、Plk 2和Slc 7a 5）和2种靶lncRNA（Neat 1和Tug 1）在毛囊周期中差异表达。ceRNA网络由12个相互作用的miRNA-mRNA对和13个miRNA-lncRNA对组成。功能富集分析揭示了毛发生长相关信号通路的富集。此外，GSPT 1在雄激素性脱发患者中下调，可能与脱发进展相关。通过我们的分析确定的ceRNA网络可能参与调节毛囊周期。
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.