Ribosomal RNA-depleted RNA sequencing reveals the pathogenesis of refractory Mycoplasma pneumoniae pneumonia in children

Pneumonia caused by Mycoplasma pneumoniae (M. pneumoniae) is a major cause of community-acquired pneumonia in children. In some cases, M. pneumoniae pneumonia (MPP) can develop into refractory MPP (RMPP), which shows no clinical or radiological response to macrolides, and can progress to severe and complicated pneumonia. However, the pathogenesis of RMPP remains poorly understood. The present study aimed to identify target genes that could be used as biomarkers for the clinical diagnosis of early-stage RMPP through high-throughput sequencing technology. The differences in long non-coding (lnc)RNAs, mRNAs and circular (circ)RNAs were examined between whole-blood samples from two patients with non-refractory MPP (NRMPP), two patients with RMPP and three healthy children using ribosomal (r)RNA-depleted RNA-sequencing techniques and an integrated mRNA/circRNA analysis. A total of 17 lncRNAs (four upregulated and 13 downregulated), 18 mRNAs (six upregulated and 12 downregulated) and 24 circRNAs (12 upregulated and 12 downregulated) were the most significantly differentially expressed (P<0.05) between the NRMPP and RMPP groups. Upon functional analysis, the significantly differentially expressed genes encoded by the targeting mRNAs (prostaglandin-endoperoxide synthase 2, IL-8 and fos-like antigen 1) were screened and identified to be enriched in the ‘IL-17 signaling pathway’. Furthermore, the key circRNAs in the NRMPP and RMPP comparative groups were primarily enriched in ‘herpes simplex virus 1 infection’, ‘viral carcinogenesis’ and ‘RNA transport’. In the present study, a comprehensive analysis of the differences between the NRMPP and RMPP cases was performed based on rRNA-depleted RNA-sequencing techniques, and the selected genes and circRNAs may be closely associated with the complex pathogenesis of RMPP.