circHMGCS1/miR-335-5p/ITGB2调控乳腺癌MDA-MB-231细胞增殖、迁移、侵袭的机制研究

Mechanism of circHMGCS1/miR-335-5p/ITGB2 in regulating the proliferation,migration and invasion of breast cancer MDA-MB-231 cells

目的探讨环状RNA HMGCS1(circHMGCS1)/微小RNA-335-5p(miR-335-5p)/整合素β2(ITGB2)分子轴对乳腺癌(BC)MDA-MB-231细胞增殖、迁移、侵袭的影响及其可能作用机制。方法收集2020-05—2020-11于本院接受手术治疗的47例BC组织及癌旁组织(>病灶5 cm),qRT-PCR、Western blot分别检测circHMGCS1、miR-335-5p、ITGB2蛋白表达量;sh-NC、sh-circHMGCS1、miR-NC、miR-335-5p mimics分别转染至MDA-MB-231细胞;分别检测细胞活力、划痕愈合率、侵袭细胞数;双荧光素酶报告实验检测circHMGCS1与miR-335-5p、miR-335-5p与ITGB2靶向关系。结果与癌旁组织比较,BC组织中circHMGCS1、ITGB2蛋白表达量升高(P<0.05),miR-335-5p表达量降低(P<0.05);与转染sh-NC或miR-NC比较,转染sh-circHMGCS1或miR-335-5p mimics后细胞活力、划痕愈合率降低(P<0.05),侵袭细胞数减少(P<0.05);circHMGCS1靶向调控miR-335-5p表达,miR-335-5p靶向调控ITGB2表达。结论干扰circHMGCS1表达可上调miR-335-5p表达及下调ITGB2表达,进而抑制BC细胞增殖、迁移、侵袭。

Objective To investigate the effect of circular RNA HMGCS1(circHMGCS1)/microRNA-335-5p(miR-335-5p)/integrin β2(ITGB2)molecular axis on the proliferation,migration and invasion of breast cancer(BC)MDA-MB-231 cells and its possible mechanism.Methods A total of 47 BC tissues and adjacent tissues(>5 cm to the lesions)were collected in our hospital from May 2020 to November 2020.qRT-PCR and Western blot were used to detect the expression of circHMGCS1,miR-335-5p,and ITGB2 protein.sh-NC,sh-circHMGCS1,miR-NC,and miR-335-5p mimics were transfected into MDA-MB-231 cells,respectively.Cell viability,scratch healing rate,and number of invasive cells were detected respectively.The dual luciferase reporter assay was used to detect the targeting relationship between circHMGCS1 and miR-335-5p,miR-335-5p and ITGB2.Results Compared with the adjacent tissue,the protein expression of circHMGCS1 and ITGB2 in BC tissue was increased(P<0.05),while the expression of miR-335-5p was decreased(P<0.05).Compared with transfection of sh-NC or miR-NC,after transfection of sh-circHMGCS1 or miR-335-5p mimics,cell viability,wound healing rate was decreased(P<0.05),the number of invasive cells was decreased(P<0.05).circHMGCS1 targeted to regulate the expression of miR-335-5p,and miR-335-5p targeted to regulate the expression of ITGB2.Conclusion Interfering with the expression of circHMGCS1 could up-regulate the expression of miR-335-5p and down-regulate the expression of ITGB2,thereby inhibiting the proliferation,migration and invasion of BC cells.