The Circular RNA CircCOL1A1 Functions as a miR-149-5p Sponge to Regulate the Formation of Superior-Quality Brush Hair via the CMTM3/AR Axis.

Jian Wang,Xi Wu,Liuming Zhang,Yongjun Li,Qiang Wang,Jingwen Qu,Xiaomei Sun,Yanhu Wang

doi:10.3389/fcell.2022.760466

Jian Wang, Xi Wu + Show 6 more

Open Access

https://doi.org/10.3389/fcell.2022.760466

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Abstract

Superior-quality brush hair, also called Type III hair, can be obtained only from the cervical spine region of skin tissues of Yangtze River Delta white goats. The formation of superior-quality brush hair is controlled by a series of critical genes and related signaling pathways. Circular RNAs (circRNAs) are ubiquitous endogenous noncoding RNAs that regulate many biological and physiological processes in mammals. However, little is known about the potential regulatory role of circRNAs in superior-quality brush hair formation. Here, we analyzed circRNA sequencing data from cervical spine region skin tissues of normal-quality brush hair goats and superior-quality brush hair goats and then selected and identified the differentially expressed circRNA circCOL1A1. To investigate the regulatory role and mechanism of action of circCOL1A1, goat hair follicle stem cells (gHFSCs) were cultured and treated with a circCOL1A1 overexpression plasmid and small-interfering RNAs (siRNAs). Functional assays showed that circCOL1A1 knockdown promoted the proliferation and differentiation of gHFSCs cultured in vitro but inhibited stem cell apoptosis, whereas overexpression of circCOL1A1 suppressed stem cell proliferation and differentiation and induced apoptosis. Bioinformatics analysis combined with dual-luciferase reporter assays and RNA binding protein immunoprecipitation (RIP) verified that, mechanistically, circCOL1A1 could bind miR-149-5p directly and then relieve its inhibitory effect on CMTM3 to further control the CMTM3/AR axis. Collectively, our results reveal a novel regulatory pathway for the formation of superior-quality brush hair and indicate that circCOL1A1 plays a role in gHFSC growth and superior-quality brush hair formation by targeting the miR-149-5p/CMTM3/AR axis.

Highlights

Yangtze River Delta white goats, known as Haimen goats or Brush Hair goats, are an exceptional goat breed worldwide that can be used to harvest superior-quality brush hair (National livestock and Poultry Genetic Resources Committee, 2011)
These results suggested that the identified interaction networks might be closely related to superior-quality brush hair formation
The results showed that circCOL1A1 and miR-149-5p were successfully enriched in the argonaute-2 (Ago-2) protein pull-down group but not in the immunoglobulin G (IgG) protein pull-down group (Figure 6H)

Summary

Introduction

Yangtze River Delta white goats, known as Haimen goats or Brush Hair goats, are an exceptional goat breed worldwide that can be used to harvest superior-quality brush hair (National livestock and Poultry Genetic Resources Committee, 2011). 5) CMTM3 knockdown accelerates hair follicle stem cell proliferation and promotes AR expression, while overexpression of CMTM3 significantly inhibits the proliferation of stem cells and is accompanied by a reduction in the AR expression level (Wang et al, 2020; Wang et al, 2021) This critical evidence suggests that a series of protein-coding genes and noncoding RNAs (ncRNAs) are important for the formation of superior-quality brush hair. Recent studies have revealed that circRNAs have several critical regulatory functions in eukaryotes, including acting as miRNA sponges (Wang C. et al, 2019), binding to proteins (Li et al, 2019), serving as templates for translation (Legnini et al, 2017), and regulating gene transcription (Li et al, 2015) or translation (Wu et al, 2019). Little is known about circRNA functions in Yangtze River Delta white goats and the regulatory mechanism involved in superior-quality brush hair formation

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