Systematic Analysis of Non-coding RNAs Involved in the Angora Rabbit (Oryctolagus cuniculus) Hair Follicle Cycle by RNA Sequencing.

Bohao Zhao,Jiali Li,Yeyi Xiao,Yang Chen,Shuaishuai Hu,Manman Wang,Naisu Yang,Xinsheng Wu,Ming Liu

doi:10.3389/fgene.2019.00407

Abstract

The hair follicle (HF) cycle is a complicated and dynamic process in mammals, associated with various signaling pathways and gene expression patterns. Non-coding RNAs (ncRNAs) are RNA molecules that are not translated into proteins but are involved in the regulation of various cellular and biological processes. This study explored the relationship between ncRNAs and the HF cycle by developing a synchronization model in Angora rabbits. Transcriptome analysis was performed to investigate ncRNAs and mRNAs associated with the various stages of the HF cycle. One hundred and eleven long non-coding RNAs (lncRNAs), 247 circular RNAs (circRNAs), 97 microRNAs (miRNAs), and 1,168 mRNAs were differentially expressed during the three HF growth stages. Quantitative real-time PCR was used to validate the ncRNA transcriptome analysis results. Gene ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses provided information on the possible roles of ncRNAs and mRNAs during the HF cycle. In addition, lncRNA–miRNA–mRNA and circRNA–miRNA–mRNA ceRNA networks were constructed to investigate the underlying relationships between ncRNAs and mRNAs. LNC_002919 and novel_circ_0026326 were found to act as ceRNAs and participated in the regulation of the HF cycle as miR-320-3p sponges. This research comprehensively identified candidate regulatory ncRNAs during the HF cycle by transcriptome analysis, highlighting the possible association between ncRNAs and the regulation of hair growth. This study provides a basis for systematic further research and new insights on the regulation of the HF cycle.

Highlights

Hair follicle (HF) development is a complex morphogenetic process that relies on a variety of signaling systems, and on interactions between mesenchymal and epithelial tissues (Hardy, 1992; Oro and Scott, 1998)
The hair cycle of Angora rabbits is characterized by an anagen phase between days 0 and 110, a catagen phase between days 120 and 130, and a telogen phase between days 140 and 150
The HF synchronization model can contribute to the field of research in the chronobiology of HFs. non-coding RNA (ncRNA) are epigenetic, translational and genetic regulators that may play a role in numerous biological processes in eukaryotes (Mattick and Makunin, 2006). ncRNAs could play complicated and vital roles during the hair cycle; investigation of the regulatory and functional interactions between long non-coding RNAs (lncRNAs), circRNAs, miRNAs, and mRNAs may increase understanding of this biological process

Summary

Introduction

Hair follicle (HF) development is a complex morphogenetic process that relies on a variety of signaling systems, and on interactions between mesenchymal and epithelial tissues (Hardy, 1992; Oro and Scott, 1998). The immediate removal of hair shafts could induce homogeneous anagen development in the murine model, which leads to the spontaneous entering of consecutive stages (catagen and telogen). In this way, the methods for the analysis of murine HF growth were provided, and were based on histologic and ultrastructural studies on murine hair cycling (Veen et al, 1999; Müller-Röver et al, 2001). HFs enter the telogen phase, where hair shafts stop growing, and begin to fall due to synthesis and release of hair cycle inhibitor (Stenn and Paus, 2001). The molecular mechanisms underlying the regulation of the hair cycle and of HF development are of interest in medicine and developmental biology (Shirokova et al, 2016; Ahmed et al, 2017; Sardella et al, 2017)

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