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Construct a circRNA/miRNA/mRNA regulatory network to explore potential pathogenesis and therapy options of clear cell

Shuheng Bai1, YinYing Wu2, Yanli Yan1

  • 1Department of Radiotherapy, Oncology Department, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi Province, China.

Scientific Reports
|August 14, 2020
PubMed

Insights

This study reveals a novel circRNA/miRNA/mRNA regulatory network in clear cell renal cell carcinoma (ccRCC), identifying key genes and potential therapeutic drugs like capecitabine for ccRCC treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Bioinformatics

Background:

  • Clear cell renal cell carcinoma (ccRCC) is the predominant subtype of kidney cancer.
  • Circular RNAs (circRNAs) function as competing endogenous RNAs (ceRNAs) regulating microRNAs (miRNAs) in various cancers.
  • The precise role of the circRNA/miRNA/mRNA regulatory network in ccRCC pathogenesis remains largely uncharacterized.

Purpose of the Study:

  • To elucidate the complex circRNA/miRNA/mRNA regulatory network in ccRCC.
  • To identify key molecular players and potential therapeutic targets within this network.
  • To explore potential drug candidates for ccRCC treatment based on the identified network.

Main Methods:

  • Differential expression analysis of circRNAs from GEO datasets.
  • Prediction of miRNA targets using databases like Cancer-specific circRNA and Circular RNA Interactome.
  • Identification of target genes through miRWalk and TCGA data integration.
  • Construction of a protein-protein interaction (PPI) network using Cytoscape and DAVID.
  • Survival analysis of hub genes using GEPIA.
  • Drug and compound screening via CMap and PharmGKB.

Main Results:

  • Six differentially expressed circRNAs and six regulatory miRNAs were identified.
  • A network involving 497 genes regulated by these miRNAs was established, linked to cancer-related functions.
  • Ten hub genes were identified, with PTGER3, ADCY2, CXCL5, GRM4, and APLN significantly impacting ccRCC patient survival.
  • Potential therapeutic agents, including josamycin and drugs like capecitabine, were predicted.

Conclusions:

  • The study establishes a comprehensive circRNA/miRNA/mRNA regulatory network critical to ccRCC.
  • Specific circRNAs, miRNAs, and hub genes (e.g., PTGER3, ADCY2) are implicated in ccRCC progression and patient survival.
  • Identified compounds and drugs offer promising avenues for novel ccRCC therapeutic strategies.

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