miR-377在宫颈癌中的表达及其对宫颈癌细胞增殖、侵袭和EMT的影响

Expression of miR-377 in cervical cancer and its effect on proliferation,invasion and EMT of cervical cancer cells

目的 观察miR-377在宫颈癌组织和细胞中的表达,探讨miR-377对宫颈癌发展的影响。方法 检测miR-377在宫颈癌组织和Hela、SiHa和Caski细胞、H8细胞中的表达;过表达或下调miR-377后,CCK-8、细胞侵袭实验、Western blot和细胞划痕愈合实验分别检测miR-377对Hela细胞增殖、侵袭、上皮间质转化(EMT)和迁移能力的影响。下调CUL4A表达后,检测Hela细胞增殖、侵袭、迁移和EMT;Western blot检测过表达CUL4A对cAMP/PKA通路的影响。结果 miR-377在宫颈癌组织的表达(0.58±0.24)低于癌旁正常组织(1.05±0.35),miR-377在宫颈癌Hela、Siha和Caski细胞中的表达(0.36±0.09、0.72±0.18、0.75±0.37)低于H8细胞(1.43±0.28),差异均有统计学意义(P<0.01)。过表达miR-377抑制了Hela细胞增殖、侵袭、迁移与EMT,下调miR-377则起到相反作用。miR-377靶向和负调控CUL4A,下调CUL4A抑制了Hela细胞发展;过表达CUL4A激活了细胞内cAMP/PKA通路,并利用该通路促进Hela细胞发展。结论 miR-377负调控CUL4A激活cAMP/PKA通路,抑制宫颈癌细胞的增殖、侵袭、迁移和EMT。

Objective To observe the expression of miR-377 in cervical cancer tissues and cells,and to explore the influence of miR-377 on the development of cervical cancer.Methods The expression of miR-377 in cervical cancer tissues,Hela,SiHa,Caski cells and H8 cells was detected.After overexpression or down-regulation of miR-377,CCK-8,cell invasion test,Western blot and cell scratch healing test were used to detect the effects of miR-377 on Hela cells’ proliferation,invasion,epithelial mesenchymal transformation(EMT),and migration ability.After down-regulation of CUL4 A expression,Hela cell proliferation,invasion,migration and EMT were detected,and the effect of overexpression of CUL4 A on cAMP/PKA pathway was detected by Western blot.Results The expression of miR-377 in cervical cancer tissues(0.58±0.24) was lower than that in adjacent normal tissues(1.05±0.35).The expression of miR-377 in Hela,Siha and Caski cells(0.36±0.09,0.72±0.18,0.75±0.37) was lower than that in H8 cells(1.43±0.28).The differences were statistically significant(P<0.01).Overexpression of miR-377 inhibited Hela cell proliferation,invasion,migration and EMT,while down-regulation of miR-377 had the opposite effect.miR-377 targeted and negatively regulated CUL4 A,and down-regulation of CUL4 A inhibited Hela cell development.Overexpression of CUL4 A activated the cAMP/PKA pathway and promoted the development of Hela cells through the pathway.Conclusions miR-377 negatively regulates CUL4 A to activate cAMP/PKA pathway,and inhibits the proliferation,invasion,migration and EMT of cervical cancer.