Circ_0006944 aggravates LPS-induced HK2 cell injury via modulating miR-205-5p/UBL4A pathway

Autoimmunity. 2023 Dec;56(1):2276066. doi: 10.1080/08916934.2023.2276066. Epub 2023 Nov 22.

Abstract

Circular RNAs (circRNAs) has been manifested to be involved in the development of human diseases, including sepsis-associated acute kidney injury (SA-AKI). However, the function and mechanism of circ_0006944 in SA-AKI has not been validated. Lipopolysaccharide (LPS) was utilised to induce AKI cell model. Levels of genes and proteins were monitored by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. Cell counting kit 8 assay, EdU assay and flow cytometry were exploited to estimate cell proliferation and apoptosis. The concentrations of inflammation factors were measured via using ELISA assay. The levels of MDA and SOD were tested by the corresponding kits. The relationship between miR-205-5p and circ_0006944 or UBL4A was verified by dual-luciferase reporter assay and RIP assay. Circ_0006944 was overexpressed in SA-AKI patients, and interference of circ_0006944 restrained LPS-stimulated HK2 cell proliferation repression, apoptosis, inflammation and oxidative stress. Mechanistically, circ_0006944 could sponge miR-205-5p, and miR-205-5p interference counteracted circ_0006944 inhibition-mediated impact on the biological functions in LPS-induced HK2 cell. Additionally, UBL4A was targeted by miR-205-5p, and UBL4A overexpression also partially abolished the repressive impacts of miR-205-5p on LPS-triggered HK2 cell damage. Importantly, circ_0006944 sponged miR-205-5p to mediate the expression of UBL4A. Our outcomes identified that circ_0006944 exacerbated SA-AKI development via miR-205-5p/UBL4A axis, which might be a potential treatment and diagnosis biomarker for SA-AKI.

Keywords: SA-aki; UBL4A; circ_0006944; miR-205-5p.

MeSH terms

  • Acute Kidney Injury* / etiology
  • Acute Kidney Injury* / genetics
  • Cell Line
  • Humans
  • Inflammation
  • MicroRNAs* / genetics
  • Oxidative Stress
  • RNA, Circular* / genetics
  • Sepsis* / complications
  • Ubiquitins* / genetics

Substances

  • RNA, Circular
  • MIRN205 microRNA, human
  • Ubl4A protein, human
  • MicroRNAs
  • Ubiquitins