1. Academic Validation
  2. Melatonin Regulates lncRNA NEAT1/miR-138-5p/HIF-1α Axis through MOV10 to Affect Acid-Related Esophageal Epithelial Cell Pyroptosis

Melatonin Regulates lncRNA NEAT1/miR-138-5p/HIF-1α Axis through MOV10 to Affect Acid-Related Esophageal Epithelial Cell Pyroptosis

  • Pharmacology. 2023 May 12;1-15. doi: 10.1159/000530090.
Xin Su 1 Wenjie Li 2 Danping Zhang 2 Hong Zhu 2
Affiliations

Affiliations

  • 1 Department of Gastroenterology, Jiangsu Province Hospital and the First Affiliated Hospital of Nanjing Medical University, Nanjing, China, 1355324949@qq.com.
  • 2 Department of Gastroenterology, Jiangsu Province Hospital and the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Abstract

Introduction: Acid-related inflammatory damage to the esophageal epithelium is a key component in the development of gastroesophageal reflux disease. Melatonin (MT) is considered as a potential therapeutic agent, but its molecular mechanism is unknown.

Methods: The expression of HIF-1α and pyroptosis-related genes (NLRP3, Caspase-1, IL-1β, and IL-18) was analyzed using bioinformatics methods in GSE63401 and validated using quantitative real-time polymerase chain reaction and Western blot in an HEEC inflammation model induced by deoxycholic acid (DCA). Hoechst 33342/PI double staining was used to assess the level of Pyroptosis, and the effect of MT treatment was observed. The miRDB, TarBase, miRcode, miRNet, and ENCORI databases were used to predict the long non-coding RNA (lncRNA) targeting HIF-1α and the RNA-binding protein interacting with the lncRNA.

Results: The expressions of Moloney leukemia virus 10 (MOV10), lncRNA NEAT1, HIF-1α, and pyroptosis-related genes were upregulated, while the expression of miR-138-5p was downregulated in acidic DCA-induced HEEC inflammation. MOV10 may bind to lncRNA NEAT1 and stabilize its expression, while lncRNA NEAT1 upregulates the expression of HIF-1α by adsorbing miR-138-5p to activate the NLRP3 inflammasome. However, MT pretreatment can significantly inhibit these processes.

Conclusions: MOV10-lncRNA NEAT1/miR-138-5p/HIF-1α/NLRP3 axis plays a crucial role in acid-related esophageal epithelial inflammatory injury, and MT may exert an esophageal protective effect by inhibiting the pathway.

Keywords

Competitive endogenous RNA; Deoxycholic acid; Gastroesophageal reflux disease; HIF-1α; Melatonin; NLRP3; RNA-binding protein.

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