Mechanism of lncRNA-XIST Targeting miR-592/PIK3CA on Nude Mice with Breast Cancer Cells
Objective:To investigate the mechanism of action of lncRNA-XIST targeting miR-592/PIK3CA on nude mice with breast cancer cells.Methods:The expression levels of lncRNA XIST,miR-592 and PIK3CA were compared in 20 breast cancer tissues and adjacent tissues collected in our hospital from January 2021 to 2022.MCF-10A,MCF-7,BT-549,MDA-MB-468,HSS578T cells were cultured,and the expressions of lncRNA XIST,miR-592 and PIK3CA in different breast cancer cells were compared.The trans-planted tumor model of MCF-7 nude mice was established,and the mice were divided into control group,si-NC group,si-XIST group,pcDNA-NC group and pcDNA-XIST group,and the survival status,tumor volume and tumor inhibition rate of each group were com-pared.Western blot was used to detect the expression of MMP-2,MMP-9 and Bax proteins,and then double luciferase reporter gene as-say was performed.Results:In breast cancer tissues,the expression level of lncRNA XIST was lower,and the expression levels of miR-592 and PIK3CA were higher(P＜0.05).Compared with MCF-10A normal breast cancer cells,the expression of lncRNA XIST in MCF-7 breast cancer cells was the lowest,and the expression of miR-592 and PIK3CA was the highest.MCF-7 breast cancer cells were selected as the research objects for follow-up studies.There was no statistical significance in tumor volume and weight in control group,si-NC group and pcDNA-NC group,and no significance in tumor inhibition rate between si-NC group and pcDNA-NC group(P＞0.05).The tumor volume and weight of the si-XIST group were increased(P＜0.05),and the tumor inhibitory rate was-40.04±5.24％;the tu-mor volume and weight of the pcDNA-XIST group were decreased(P＜0.05),and the tumor inhibitory rate was 54.29±7.89％.There was no significance in MMP-2,MMP-9 and Bax of control group,si-NC group and pcDNA-NC group(P＞0.05).Compared with control group,si-NC group and pcDNA-NC group,MMP-2 and MMP-9 in si-XIST group were significantly increased,and Bax was significantly decreased,MMP-2 and MMP-9 were significantly decreased,and Bax was increased in pcDNA-XIST group(P＜0.05).Compared with mimic NC,the fluorescence activity of XIST-WT and PIK3CA-WT cells in miR-592 mimic group was decreased(P＜0.05),and there was no significance in the fluorescence activity of XIST-MUT and PIK3CA-MUT cells between the two groups(P＞0.05).Conclusion:Over-expression of XIST may regulate PIK3CA expression level by sponging miR-592,reduce MMP-2,MMP-9 levels and increase Bax lev-els,and subsequently inhibit the growth of subcutaneous xenograft tumors in MCF-7 nude mice.
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