阿托伐他汀钙对人脐静脉内皮细胞增殖迁移的影响观察、关键靶基因及其相关lncRNA筛选OACSTPCD

Objective To observe the effects of atorvastatin calcium on the cell proliferation and migration of human umbilical vein endothelial cells(HUVECs),and to screen the hub mRNA and co-related long non-coding RNA(lncRNA)of atorvastatin calcium on HUVECs.Methods HUVECs in the logarithmic growth phase were divided into the group 1 and group 2.Cells in the group 1 and group 2 were treated with 5 μmol/L atorvastatin calcium and the same amount of PBS for 24 h,respectively.① Observation of effects of atorvastatin calcium on the cell proliferation and migration of HUVECs:The cell cycle was measured by flow cytometry,the cell proliferation was observed by CCK-8 method,and the cell migra-tion was observed by scratch healing test.② Screening of hub mRNAs and co-related lncRNAs in HUVECs treated with atorvastatin calcium:illumina platform was used to detect mRNA and lncRNA in cells of the two groups.Differentially ex-pressed mRNAs and lncRNAs with|log2 Fold change|>1.5 and P adjusted<0.05 were screened using limma package in R Studio software.Gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis were used to analyze the biological functions of differentially expressed mRNAs.The STRING database was used to analyze the protein interaction of differentially expressed mRNAs.The CytoNCA plug-in was used to screen the top 10 hub mRNAs with the highest mediation centrality,and the co-expressed lncRNAs with the hub mRNAs with Pearson correlation coeffi-cient>0.99 were screened.Real-time fluorescence quantitative PCR(qPCR)was used to detect the hub mRNA and its co-expressed lncRNA in the two groups.Results Compared with the group 2,the proportion of cells in the G0/G1 phase of the group 1 was higher,the cell proliferation was inhibited,and the cell migration area was smaller after 24 h of culture(all P<0.05).Compared with the group 2,there were 1 510 differentially expressed mRNAs and 744 differentially ex-pressed lncRNAs in the group 1;the biological functions of differentially expressed mRNAs involved 294 GO sets and 27 KEGG pathways;there were 10 hub mRNAs and 130 lncRNAs co-expressed with them,including AC017101.1,AC125257.1,AC004846.1,etc.Compared with the group 2,the relative expression levels of HSP90AA1,CDK4,CCND1,PLK1,and PCNA in the group 1 were lower,and the relative expression levels of AC017101.1,AC125257.1,AC004846.1,and AL390719.1 were higher(all P<0.05).Conclusions Atorvastatin calcium can block the HUVECs in the G0/G1 phase and inhibit their proliferation and migration.There are 10 hub mRNAs such as HSP90AA1,CDK4 and CCND1,and 130 co-related lncRNAs such as AC017101.1,AC125257.1 and AC004846.1 in atorvastatin calcium treat-ment of HUVECs.Atorvastatin calcium may promote the expression of co-related lncrnas such as AC017101.1,AC125257.1 and AC004846.1 and down-regulate the expression of HSP90AA1,CDK4 and CCND1 mRNA in HUVECs.Thus,the cell cycle of HUVECs is arrested and cell proliferation and migration are inhibited.