摘要
目的探究环状RNA UBAP2(circ-UBAP2)在急性肺损伤(ALI)A549细胞模型中的表达及作用,并阐明其潜在的分子调控机制。方法脂多糖(LPS)处理A549细胞以构建ALI细胞模型,并利用qRT-PCR检测细胞中circ-UBAP2的表达变化;将si-circ-UBAP2转染至LPS诱导的A549细胞中,采用ELISA和流式细胞术检测炎症因子的水平以及细胞凋亡;利用生物信息学分析和双荧光素酶实验明确circ-UBAP2的作用机制。结果circ-UBAP2在LPS诱导的A549细胞中高表达(P<0.01),沉默circ-UBAP2能够促进LPS诱导的A549细胞凋亡(P<0.01),降低炎症因子TNF-α、IL-6、IL-18和IL-1β的水平(P均<0.01)。circ-UBAP2可以竞争性结合miR-34a-5p,沉默circ-UBAP2能够促进LPS诱导的A549细胞中miR-34a-5p的表达(P<0.01)。miR-34a-5p能够靶向OGDH,过表达miR-34a-5p能够抑制LPS诱导的A549细胞中OGDH的表达(P<0.01)。沉默circ-UBAP2明显降低了MEK1和MEK1/2的磷酸化水平,但上述抑制作用被miR-34a-5p抑制剂所逆转。结论LPS诱导的A549细胞中高表达的circ-UBAP2能够促进炎症反应并抑制细胞凋亡,circ-UBAP2通过miR-34a-5p/OGDH/MAPK轴调控ALI。
Objective To investigate the expression and role of circ-UBAP2 in A549 cell model of acute lung injury(ALI)and elucidate its potential molecular regulatory mechanism.Methods A549 cell was treated with LPS to construct an ALI cell model.The expression of circ-UBAP2 in cell was detected by qRT-PCR.To explore the effect of circ-UBAP2 on LPS-induced A549 cell,si-circ-UBAP2 was transfected into LPS-induced A549 cell,and then the level of inflammatory fac⁃tors and apoptosis were detected by ELISA and flow cytometry.Additionally,bioinformatics analysis and dual luciferase as⁃say were used to clarify the mechanism of circ-UBAP2.Results Circ-UBAP2 was highly expressed in LPS-induced A549 cell(P<0.01).Silencing circ-UBAP2 promoted LPS-induced apoptosis of A549 cells(P<0.01)and reduced the levels of inflammatory factors TNF-α,IL-6,IL-18 and IL-1β(all P<0.01).Circ-UBAP2 competitively bound to miR-34a-5p,and silencing circ-UBAP2 promoted the expression of miR-34a-5p in LPS-induced A549 cells(P<0.01).MiR-34a-5p targeted OGDH.Overexpression of miR-34a-5p inhibited the expression of OGDH in LPS-induced A549 cells(P<0.01).Silencing circ-UBAP2 significantly reduced the phosphorylation levels of MEK1 and MEK1/2,but the above inhibition was reversed by miR-34a-5p inhibitor.Conclusions The high expressed circ-UBAP2 in LPS-induced A549 cells can promote inflam⁃matory response and inhibits apoptosis.Circ-UBAP2 regulates ALI through the miR-34a-5p/OGDH/MAPK axis.
作者
薛苹苹
孙歆炜
刘雪妮
王文静
郝跃伟
XUE Pingping;SUN Xinwei;LIU Xueni;WANG Wenjing;HAO Yuewei(Department of Infectious Diseases,Shandong Second Provicial General Hospital,Jinan 250000,China;Department of Joint and Spinal Surgery,Shandong Second Provicial General Hospital,Jinan 250000,China)
出处
《老年医学研究》
2025年第3期54-58,共5页
Geriatrics Research
基金
山东省医药卫生科技发展计划项目(202110000618,环状RNA UBAP2通过miR-34a-5p/OGDH/MAPK轴调控脓毒症诱导的急性肺损伤)。
