Whole transcriptome sequencing for revealing the pathogenesis of sporotrichosis caused by Sporothrix globosa

Sci Rep. 2024 Jan 3;14(1):359. doi: 10.1038/s41598-023-50728-7.

Abstract

This study aimed to investigate the molecular mechanism of sporotrichosis and identify possible novel therapeutic targets. Total RNA was extracted from skin lesion samples from sporotrichosis patients and used to construct a long-chain RNA transcriptome library and miRNA transcriptome library for whole transcriptome sequencing. The differentially expressed genes (DEGs) between the groups were identified, and then Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and Gene Set Enrichment Analysis enrichment analyses were performed based on the DEGs. An lncRNA-miRNA-mRNA ceRNA network was constructed. The expressions of JAK/STAT pathway-related proteins were detected in the patient and control tissues using RT-qPCR and Western blot analysis. Enrichment analysis showed that the DEGs were mainly enriched in various infectious diseases and immune response-related signaling pathways. Competing endogenous RNA network analysis was performed and identified the hub lncRNAs, miRNAs, and mRNAs. Compared with the control group, the mRNA expressions of SOCS3, IL-6, and JAK3 were significantly upregulated, while the expression of STAT3 did not change significantly. Also, the protein expressions of SOCS3, IL-6, JAK3, and STAT3, as well as phosphorylated JAK3 and STAT3, were significantly upregulated. We identified 671 lncRNA DEGs, 3281 mRNA DEGs, and 214 miRNA DEGs to be involved in Sporothrix globosa infection. The study findings suggest that the JAK/STAT pathway may be a therapeutic target for sporotrichosis.

MeSH terms

  • Exome Sequencing
  • Gene Regulatory Networks
  • Humans
  • Interleukin-6 / genetics
  • Janus Kinases / genetics
  • MicroRNAs* / genetics
  • RNA, Long Noncoding* / genetics
  • RNA, Messenger / genetics
  • STAT Transcription Factors / genetics
  • Signal Transduction / genetics
  • Sporotrichosis* / genetics
  • Transcriptome

Substances

  • RNA, Long Noncoding
  • Interleukin-6
  • Janus Kinases
  • STAT Transcription Factors
  • MicroRNAs
  • RNA, Messenger

Supplementary concepts

  • Sporothrix globosa