环状RNA circ_0000285通过吸附miR-127调控VAMP2水平参与卵巢癌进展

circ_0000285 regulates VAMP2 through sponging miR-127 and participates in the development of ovarian cancer

目的探讨circ_0000285/miR-127/VAMP2轴对卵巢癌(ovarian cancer,OC)细胞增殖、侵袭的影响。方法采用qRT-PCR对OC患者癌组织和癌旁组织中的circ_0000285、miR-127和VAMP2的表达进行检测,对circ_0000285和miR-127及circ_0000285和VAMP2的相关性进行分析。双荧光素酶报告实验(dual luciferase reporter assay)验证miR-127和circ_0000285/VAMP2之间的靶向关系。MTT和Transwell法分别检测细胞增殖活力和侵袭情况。结果相对癌旁组织,OC组织样本中miR-127表达水平明显下降,circ_0000285和VAMP2表达增强,miR-127与circ_0000285和VAMP2表达均呈负相关(r=-0.5348,P<0.0001;r=-0.3766,P<0.0001)。相对于si-NC组在24 h、48 h和72 h的增殖活力(0.47±0.03)(0.79±0.05)(1.16±0.09)和侵袭(100.00±12.33),敲除circ_0000285能抑制OC细胞增殖(0.28±0.02)(0.51±0.04)(0.78±0.06)和侵袭(49.22±5.08)(均P<0.05)。过表达miR-127同样能抑制OC细胞增殖、侵袭,但该作用能被circ_0000285部分挽救。circ_0000285对OC进展的促进可能是通过miR-127/VAMP2轴实现的。结论circRNA circ_0000285能调控miR-127/VAMP2轴参与OC的进展,下调circRNA circ_0000285表达可抑制OC细胞增殖和侵袭能力,circ_0000285有望在OC疾病的靶向治疗中发挥作用。

Objective To investigate the effects of circ_0000285/miR-127/VAMP2 axis on proliferation and invasion of ovarian cancer(OC)cells.Methods Real-time quantitative polymerase chain reaction(qRT-PCR)was used to detect the expression of circ_0000285,miR-127 and VAMP2 in tissue with OC and normal tissue respectively,and the correlation circ_0000285/miR-127/VAMP2 was analyzed by correlation analysis.Dual luciferase reporter assay was used to verify the targeting relationship between miR-127 and circ_0000285/VAMP2.Cell proliferation and invasion were subsequently detected by MTT and Transwell assay.Results Compared with the paracancerous tissue,the expression of miR-127 was significantly decreased,while the expression of circ_0000285 and VAMP2 was increased in OC tissue.miR-127 was negatively correlated with circ_0000285 and VAMP2(r=-0.5348,P<0.0001;r=-0.3766,P<0.0001).Compared with proliferative activity at 24 h,48 h,72 h(0.47±0.03)(0.79±0.05)(1.16±0.09)and invasion(100.00±12.33)in si-NC group,knocking down of circ_0000285 inhibited the proliferation(0.28±0.02)(0.51±0.04)(0.78±0.06)and invasion(49.22±5.08)of OC cells(all P<0.05).Overexpression of miR-127 could also restrain proliferation,invasion of OC cells,but this effect can be partly saved by circ_0000285.The regulation circ_0000285 on OC may be realized through miR-127/VAMP2.Conclusions circ_0000285 participates in the progression of ovarian cancer via regulating miR-127/VAMP2 axis.Down-regulating the expression of circ_0000285 inhibits the proliferation and invasion of ovarian cancer cells,circ_0000285 is expected to play a role in the targeted therapies of OC.