lncRNA MNX1-AS1通过靶向调控miR-744-5p/PHB2轴促进非小细胞肺癌细胞的恶性表型OA

AIM:To investigate the impact of long noncoding RNA(lncRNA)MNX1-AS1 on the viability,migration and invasion of non-small-cell lung cancer(NSCLC)cells,through its modulation of the microRNA-744-5p(miR-744-5p)/prihibitin 2(PHB2)axis.METHODS:The expression of MNX1-AS1,miR-744-5p and PHB2 mRNA in primary tumor tissues and adjacent normal tissues from 160 patients with NSCLC were measured using RT-qPCR.Cell lines with stable transfection were established,and the H1299 cells were divided into the following groups:blank control,sh-NC,sh-MNX1-AS1,sh-MNX1-AS1+miR-NC,sh-MNX1-AS1+inhibitor,mimic-NC,miR-744-5p mimic,miR-744-5p mimic+pcDNA,and miR-744-5p mimic+pcDNA-PHB2.Dual-luciferase reporter assay was performed to verify the targeting relationships between miR-744-5p and MNX1-AS1 as well as miR-744-5p and PHB2.Methyl thiazolyl tetrazolium(MTT)assay,Transwell assays and Western blot were employed to evaluate the effects of MNX1-AS1 targeting miR-744-5p and miR-744-5p targeting PHB2 on the viability,migration and invasion of NSCLC cells.RESULTS:Compared with adja-cent tissues and normal lung epithelial cells,the expression levels of MNX1-AS1 and PHB2 mRNA were significantly up-regulated in NSCLC tissues and cell lines,while miR-744-5p was significantly down-regulated(P<0.05).Dual-luciferase reporter assay demonstrated that miR-744-5p was negatively regulated by MNX1-AS1 through direct targeting(P<0.05).Silencing of MNX1-AS1 significantly up-regulated miR-744-5p expression,thereby inhibiting the viability,migration and invasion of H1299 cells,concomitant with the down-regulation of vimentin and the up-regulation of E-cadherin(P<0.05).Conversely,simultaneous down-regulation of MNX1-AS1 and miR-744-5p promoted the viability,migration and invasion of H1299 cells,alongside a marked increase in vimentin and PHB2 expression and a decrease in E-cadherin(P<0.05).Furthermore,up-regulation of miR-744-5p inhibited PHB2 expression and suppressed H1299 cell viability,migration and invasion(P<0.05).However,co-overexpression of miR-744-5p and PHB2 reversed these effects,thereby promoting the viability,migration and invasion of H1299 cells(P<0.05).CONCLUSION:MNX1-AS1 promotes the viability,migra-tion and invasion of NSCLC cells by targeting the miR-744-5p/PHB2 axis,which may serve as a potential target for the clinical diagnosis and treatment of NSCLC.