Aberrant long non-coding RNA cancer susceptibility 15 (CASC15) plays a diagnostic biomarker and regulates inflammatory reaction in neonatal sepsis

Bioengineered. 2021 Dec;12(2):10373-10381. doi: 10.1080/21655979.2021.1996514.

Abstract

Neonatal sepsis (NS) is one of the important causes of neonatal death. There are many studies to confirm the role of long non-coding RNA (lncRNA) in neonatal infectious diseases. This study aimed to explore the level of cancer susceptibility 15 (CASC15) and its effect on inflammatory response in NS. Seventy-nine neonatal pneumonia (NP) patients and 80 NS patients were enrolled in this study. Reverse Transcription-quantitative PCR (RT-qPCR) was used to determine the expression levels of CASC15 and miR-144-3p. Receiver operating characteristic (ROC) curve was drawn to evaluate the diagnostic value of CASC15 in NS. RAW264.7 cells were stimulated with LPS to simulate the inflammatory response in NS patients, and the regulation and mechanism of CASC15 on the inflammatory response were explored in this in vitro cell model. Serum CASC15 was upregulated in NS patients, and it had the ability to distinguish NS patients from NP patients. LPS stimulation increased the expression of CASC15 and simultaneously stimulated the secretion of inflammatory cytokines, while the knockdown of CASC15 alleviated the inflammatory response induced by LPS stimulation. Besides, serum miR-144-3p was reduced in NS patients, and luciferase reporter genes showed that miR-144-3p was a direct target of CASC15. Overexpression of CASC15 may promote the inflammatory response of NS by targeted regulating the expression of miR-144-3p, which may provide us with new insights in the treatment of NS.

Keywords: CASC15; Neonatal sepsis; inflammation; miR-144-3p.

MeSH terms

  • Animals
  • Base Sequence
  • Biomarkers / blood
  • Female
  • Gene Expression Regulation
  • Gene Knockdown Techniques
  • Humans
  • Infant, Newborn
  • Inflammation / blood
  • Inflammation / genetics*
  • Lipopolysaccharides
  • Male
  • Mice
  • MicroRNAs / genetics
  • MicroRNAs / metabolism
  • Neonatal Sepsis / blood
  • Neonatal Sepsis / diagnosis*
  • Neonatal Sepsis / genetics*
  • RAW 264.7 Cells
  • RNA, Long Noncoding / blood
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*

Substances

  • Biomarkers
  • Lipopolysaccharides
  • MIRN144 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding

Grants and funding

The author(s) reported there is no funding associated with the work featured in this article.