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Research Paper|Volume 13, Issue 9|pp 13211—13224

Circular RNA Plek promotes fibrogenic activation by regulating the miR-135b-5p/TGF-βR1 axis after spinal cord injury

Wenzhao Wang1, Dong He3, Jianan Chen4, Zhengdong Zhang1,5, Shaoyi Wang2, Yunpeng Jiang2, Jianlu Wei2
  • 1Orthopedic Research Institute, Department of Orthopedics, West China Hospital,Sichuan University, Chengdu, Sichuan, China
  • 2Department of Orthopedics, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China
  • 3Department of Neurology, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China
  • 4Department of Orthopedics, Cheeloo College of Medicine, Jinan Central Hospital Affiliated to Shandong University, Jinan, Shandong, China
  • 5Department of Orthopedics, The First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan, China
Received: February 15, 2021Accepted: April 5, 2021Published: May 11, 2021

Copyright: © 2021 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Objectives: The spinal cord rarely repairs itself when damaged; however, methods for encouraging nerves to regrow are on the horizon. Although circular RNAs (circRNAs) contribute to various biological processes, including neuronal processes, their functions in the subacute phase of spinal cord injury (SCI) have not been elucidated. In this study, we identified a novel circRNA, named CircPlek, with increased expression in spinal tissues after SCI.

Materials and Methods: We predicted a regulatory relationship between CircPlek and miR-135b-5p, which showed the most obvious decrease in post-SCI expression. We established the CircPlek/miR-135b-5p/transforming growth factor-beta receptor type I (TGF-βR1) axis using a bioinformatics approach and further evaluated the potential function of the interaction network in vitro.

Results: We confirmed that in TGF-β1-induced fibroblasts, the overexpression of miR-135b-5p or/and inhibition of CircPlek inhibited fibrosis activation via the Smad pathway. Inhibitors of miR-135b-5p had antagonistic effects on CircPlek.

Conclusions: the CircPlek/miR-135b-5p/TGF-βR1 axis may exert important functions in SCI and is a potential therapeutic target.