Effect of circular RNA 0006750 regulating miR-876-3p on sepsis-associated acute kidney injury
WANG Huifang
MA Yuanyuan
ZHANG Xin
CHEN Kaiwen
ZHANG Xiaoli
ZHAO Jianrong
WANG Xiaoyin
Abstract：Objective To investigate whether circular RNA 0006750(circ_0006750)influences the progression of sepsis-associated acute kidney injury(SAKI)by targeting microRNA-876-3p(miR-876-3p).Methods Human kidney cortical proximal tubule epithelial cells(HK2)were cultured for 24 h with LPS at concentrations of 0,2.5,5,and 10 μg/mL to establish the SAKI models.Real-time quantitative PCR was used to measure the expression levels of circ_0006750 and miR-876-3p in cells treated with each LPS concentration.Spearman correlation analysis was performed to assess the re-lationship between circ_0006750 and miR-876-3p.Additionally,10 μg/mL LPS-induced SAKI model cells were divided into six groups and transfected with sh-NC vector(interference control group),sh-circ_0006750 vector(circ_0006750 in-terference group),sh-circ_0006750 vector+miR-876-3p inhibitor(circ_0006750 and miR-876-3p co-interference group),NC-OE vector(overexpression control group),circ_0006750-OE vector(circ_0006750 overexpression group),and circ_0006750-OE vector+miR-876-3p mimic(circ_0006750 and miR-876-3p co-overexpression group).Cell prolif-eration was assessed using CCK-8 assay at 24,48,and 72 h of culture.Apoptosis in each group was observed using flow cytometry,and tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),IL-6,reactive oxygen species(ROS),and malondialdehyde(MDA)levels were measured in each group.The targeted relationship between circ_0006750 and miR-876-3p in HK2 cells was validated using luciferase reporter gene and RNA pull-down assays.Results With the increas-ing concentrations of LPS,the relative expression of circ_0006750 in HK2 cells decreased,while the relative expression of miR-876-3p increased(both P<0.05).In the SAKI model,the expression of circ_0006750 and miR-876-3p showed a negative correlation(r=-0.795,P=0.015).Compared with the interference control group,the circ_0006750 interfer-ence group exhibited decreased OD values at 24,48,and 72 h of culture,increased apoptosis rate,and elevated levels of cellular TNF-α,IL-1β,IL-6,ROS,and MDA(all P<0.05).Compared with the circ_0006750 interference group,the circ_0006750 and miR-876-3p co-interference group exhibited increased OD values at 24,48,and 72 h,decreased apop-tosis rate,and reduced levels of cellular TNF-α,IL-1β,IL-6,ROS,and MDA(all P<0.05).Compared with the overex-pression control group,the circ_0006750 overexpression group exhibited elevated OD values at 24,48,and 72 h,re-duced apoptosis rate,and decreased levels of cellular TNF-α,IL-1β,IL-6,ROS,and MDA(all P<0.05).Compared with the circ_0006750 overexpression group,the circ_0006750 and miR-876-3p co-overexpression group exhibited de-creased OD values at 24,48,and 72 h,increased apoptosis rate,and elevated levels of cellular TNF-α,IL-1β,IL-6,ROS,and MDA(all P<0.05).The circ_0006750 directly interacted with miR-876-3p and suppressed its expression through sponge adsorption.Conclusion The circ_0006750 may promote HK-2 cell proliferation,suppress apoptosis,in-flammatory response,and oxidative stress by targeting miR-876-3p,thereby delaying the progression of SAKI.
Keywords：circular RNA 0006750miR-876-3psepsis-associated acute kidney injuryinflammatory responseoxidative stress
Publication Date：2025-09-25
Online Publishing Date：2025-10-22(First online date of this platform, not the publication date of the document)
Pages：6( 40-45 )