BACKGROUND Systemic lupus erythematosus(SLE)is a chronic autoimmune disorder impacting multiple organs,influenced by genetic factors,especially those related to the immune system.However,there is a need for new biomar...BACKGROUND Systemic lupus erythematosus(SLE)is a chronic autoimmune disorder impacting multiple organs,influenced by genetic factors,especially those related to the immune system.However,there is a need for new biomarkers in SLE.MicroRNA-125a(miR-125a)levels are decreased in T cells,B cells,and dendritic cells of SLE patients.MiR-125a plays a regulatory role in controlling the levels of tumor necrosis factor-alpha(TNF-α)and interleukin 12(IL-12),which are crucial pro-inflammatory cytokines in SLE pathogenesis.AIM To assess the levels of miR-125a,IL-12,and TNF-αin SLE patients’plasma,evaluating their diagnostic and prognostic value.METHODS The study included 100 healthy individuals,50 newly diagnosed(ND),and 50 SLE patients undergoing treatment.The patients were monitored for a duration of 24 wk to observe and record instances of relapses.MiR-125a expression was measured using real-time reverse transcription polymerase chain reaction,while ELISA kits were used to assess IL-12 and TNF-αproduction.RESULTS The results showed significantly reduced miR-125a expression in SLE patients compared to healthy individuals,with the lowest levels in ND patients.TNF-αand IL-12 expression levels were significantly elevated in SLE patients,especially in the early stages of the disease.Receiver operating characteristic curve analyses,and Cox-Mantel Log-rank tests indicated miR-125a,TNF-α,and IL-12 as proper diagnostic biomarkers for SLE.A negative correlation was found between plasma miR-125a expression and IL-12/TNF-αlevels in SLE patients.CONCLUSION Decreased miR-125a levels may be involved in the development of SLE,while elevated levels of IL-12 and TNF-αcontribute to immune dysregulation.These findings offer new diagnostic and prognostic markers for SLE.Moreover,the negative correlation observed suggests an interaction between miR-125a,TNF-α,and IL-12.Further research is necessary to uncover the underlying mechanisms that govern these relationships.展开更多
基金the Department of Research and Technology at Golestan University of Medical Sciences,No.113017.
文摘BACKGROUND Systemic lupus erythematosus(SLE)is a chronic autoimmune disorder impacting multiple organs,influenced by genetic factors,especially those related to the immune system.However,there is a need for new biomarkers in SLE.MicroRNA-125a(miR-125a)levels are decreased in T cells,B cells,and dendritic cells of SLE patients.MiR-125a plays a regulatory role in controlling the levels of tumor necrosis factor-alpha(TNF-α)and interleukin 12(IL-12),which are crucial pro-inflammatory cytokines in SLE pathogenesis.AIM To assess the levels of miR-125a,IL-12,and TNF-αin SLE patients’plasma,evaluating their diagnostic and prognostic value.METHODS The study included 100 healthy individuals,50 newly diagnosed(ND),and 50 SLE patients undergoing treatment.The patients were monitored for a duration of 24 wk to observe and record instances of relapses.MiR-125a expression was measured using real-time reverse transcription polymerase chain reaction,while ELISA kits were used to assess IL-12 and TNF-αproduction.RESULTS The results showed significantly reduced miR-125a expression in SLE patients compared to healthy individuals,with the lowest levels in ND patients.TNF-αand IL-12 expression levels were significantly elevated in SLE patients,especially in the early stages of the disease.Receiver operating characteristic curve analyses,and Cox-Mantel Log-rank tests indicated miR-125a,TNF-α,and IL-12 as proper diagnostic biomarkers for SLE.A negative correlation was found between plasma miR-125a expression and IL-12/TNF-αlevels in SLE patients.CONCLUSION Decreased miR-125a levels may be involved in the development of SLE,while elevated levels of IL-12 and TNF-αcontribute to immune dysregulation.These findings offer new diagnostic and prognostic markers for SLE.Moreover,the negative correlation observed suggests an interaction between miR-125a,TNF-α,and IL-12.Further research is necessary to uncover the underlying mechanisms that govern these relationships.
文摘目的探讨微RNA(miR)-125a抑制角质形成细胞增殖的相关机制。方法用白细胞介素(IL)-23干预处理人永生化角质形成细胞(HaCaT)24 h后,分为miR-125a组和miR-NC组,分别转染miR-125a过表达质粒和过表达对照质粒。采用细胞计数试剂盒(CCK8)法检测两组转染后0、24、48、72 h HaCaT细胞增殖能力,采用实时荧光定量PCR检测转染后24 h两组miR-125a及IL-23受体(IL-23R)mRNA的表达,采用Western印迹法测定两组转染后48 h IL-23R、Janus激酶2(JAK2)、蛋白激酶B(AKT)和磷酸化AKT(p-AKT)的表达。采用双荧光素酶报告实验验证miR-125a和IL-23R间的靶向关系。两组间均数比较采用t检验,HaCaT细胞增殖能力随时间的变化采用重复测量方差分析法评估。结果质粒转染后,miR-125a组miR-125a相对表达水平(6.377±0.745)高于miR-NC组(0.700±0.222),差异有统计学意义(t=7.305,P=0.002)。转染后0、24、48 h,miR-125a组与miR-NC组细胞增殖能力差异无统计学意义(t值分别为0.663、0.623、1.930,均P>0.05);转染后72 h,miR-125a组细胞增殖能力显著低于miR-NC组(t=4.407,P<0.05)。MiR-125a组IL-23R mRNA表达水平显著低于miR-NC组(t=3.082,P<0.05)。与miR-NC组相比,miR-125a组IL-23R、JAK2和p-AKT蛋白表达量均降低,差异有统计学意义(t值分别为11.715、6.996、12.424,P值分别<0.001、=0.002、<0.001)。双荧光素酶报告实验显示,miR-125a可靶向结合IL-23R。结论MiR-125a可能通过负性靶向调控IL-23R/JAK2/AKT信号通路抑制角质形成细胞的增殖。
