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Identifying circRNA-miRNA-mRNA Regulatory Networks in Chemotherapy-Induced Peripheral Neuropathy.

Fei Cao1, Xintong Wang1, Qingqing Ye1

  • 1Department of Anesthesiology, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou 510060, China.

Current Issues in Molecular Biology
|August 25, 2023
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Summary

Circular RNAs (circRNAs) play a crucial role in chemotherapy-induced peripheral neuropathy (CIPN). This study identified key circRNAs and immune cell interactions involved in CIPN development.

Keywords:
ceRNAchemotherapy-induced peripheral neuropathycircular RNAimmune infiltrationregulatory network

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Area of Science:

  • Molecular Biology
  • Immunology
  • Genomics

Background:

  • Chemotherapy-induced peripheral neuropathy (CIPN) is a significant adverse effect of cancer treatment.
  • The molecular mechanisms underlying CIPN, particularly the role of circular RNAs (circRNAs), are not well understood.

Purpose of the Study:

  • To investigate the association between circRNAs and CIPN.
  • To identify key circRNAs, microRNAs (miRNAs), and messenger RNAs (mRNAs) involved in CIPN pathogenesis.
  • To explore the role of the immune microenvironment in CIPN.

Main Methods:

  • Construction of CIPN models using Taxol.
  • RNA sequencing to identify differentially expressed circRNAs, long non-coding RNAs, and mRNAs.
  • Bioinformatic prediction of circRNA-miRNA-mRNA networks.
  • Functional enrichment and immune infiltration analyses.
  • Validation of hub genes using RT-qPCR.

Main Results:

  • Identified 134 differentially expressed circRNAs, 353 lncRNAs, and 86 mRNAs in CIPN models.
  • Established circRNA-miRNA-mRNA networks involving 15 circRNAs, 18 miRNAs, and 11 mRNAs.
  • Found enrichment of differentially expressed mRNAs in immune pathways, particularly involving T cells, monocytes, and macrophages.
  • Identified and validated five hub genes (Cdh1, Satb2, Fas, P2ry2, Zfhx2) correlating with specific immune cells in CIPN.
  • Predicted associated diseases, transcription factors, and potential drugs for hub genes.

Conclusions:

  • circRNAs play a critical role in the development of CIPN.
  • The immune microenvironment, including T cells and macrophages, is significantly implicated in CIPN.
  • This study provides novel insights into the molecular mechanisms of CIPN and potential therapeutic targets.