Whole-transcriptome analysis of rat cavernosum and identification of circRNA-miRNA-mRNA networks to investigate nerve injury erectile dysfunction pathogenesis

Bioengineered. 2021 Dec;12(1):6516-6528. doi: 10.1080/21655979.2021.1973863.

Abstract

There is growing evidence that circular RNAs (circRNAs) play a vital role in many kinds of diseases, including erectile dysfunction (ED). Nevertheless, the role of circRNAs in cavernous nerve-damaging ED (CNI-ED) is unknown. Here, we aimed to discover novel circRNAs, probed their potential role in the CNI-ED, and construct a ceRNA network of circRNAs. Twelve male Sprague Dawley rats were randomly divided into 2 groups by us: bilateral cavernous nerve crush (BCNC) and control groups. Four weeks after surgery, the spongy smooth muscle tissue of the rat penis was sequenced using high-throughput full transcriptome sequencing. We analyzed the expression of circRNAs, miRNAs, and mRNAs in the two groups. Twenty circRNAs with significantly different expressions were selected for RT-qPCR. CeRNA network of circRNAs was established using Cytoscape. GO and KEGG analysis was done by R package. Sequencing showed that 4,587 circRNAs, 762 miRNAs, and 21,661 mRNAs were dysregulated in the BCNC group. The top 20 differentially expressed circRNAs were further verified via RT-qPCR. The ceRNA network contained ten circRNAs, six miRNAs, and 227 mRNAs, including 23 circRNA-miRNA pairs and 227 miRNA-mRNA pairs. GO and KEGG analysis suggested that these ten circRNAs could main regulate energy metabolism processes. A protein-protein interaction network was constructed with the mRNAs in ceRNA network, and five hub genes were identified. Our study revealed a potential link between circRNAs, miRNAs, and mRNAs in CNI-ED, suggesting that circRNAs may contribute to the occurrence of ED by regulating the cellular energy metabolism in CNI-ED.

Keywords: Erectile dysfunction; bioinformatics analysis; ceRNA network; circular RNA; energy metabolism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Computational Biology
  • Energy Metabolism / genetics
  • Erectile Dysfunction* / genetics
  • Erectile Dysfunction* / metabolism
  • Male
  • Penis / innervation
  • Penis / metabolism
  • Peripheral Nerve Injuries / metabolism*
  • RNA, Circular / genetics*
  • RNA, Circular / metabolism
  • RNA, Messenger / genetics*
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Transcriptome / genetics*

Substances

  • RNA, Circular
  • RNA, Messenger

Grants and funding

This work was supported by National Natural Science Foundation of China(No. 81804092,82004360,82174376,82074433), Zhejiang Provincial Natural Science Foundation of China(No.GF20H270004, LY19H270011) and Zhejiang Provincial Key Research Project of Traditional Chinese Medicine,(No.2018ZY007).