BSN-AS2竞争性结合miR-219a-5p影响NSCLC细胞增殖、迁移、侵袭及凋亡

BSN-AS2 competitively binding miR-219a-5p to impact NSCLC proliferation,migration,invasion and apoptosis

目的:探讨BSN-AS2竞争性结合miR-219a-5p调控非小细胞肺癌(non-small cell lung cancer,NSCLC)细胞增殖、迁移、侵袭和凋亡的机制。方法:qRT-PCR检测BSN-AS2和miR-219a-5p在NSCLC组织和细胞系中的表达;原位杂交FISH检测BSN-AS2和miR-219a-5p的信号强度;双荧光素酶报告基因检验miR-219a-5p靶向调控BSN-AS2;Transwell、CCK8和Tunel细胞凋亡分别检测BSN-AS2-miR-219a-5p轴对侵袭、迁移、增殖和凋亡的影响;构建NSCLC裸鼠皮下移植瘤模型进行验证BSN-AS2-miR-219a-5p轴的调控作用。结果:BSN-AS2在NSCLC组织和细胞系中高表达,miR-219a-5p为低表达,BSN-AS2竞争性结合miR-219a-5p;siBSN-AS2组抑制NCI-H520细胞侵袭、迁移和增殖,且促进细胞凋亡,而In-miR-219a-5p组促进NCI-H520细胞侵袭、迁移和增殖,抑制细胞凋亡,siBSN-AS2+In-miR-219a-5p组相比siBSN-AS2组促进了NCI-H520细胞侵袭、迁移和增殖,抑制细胞凋亡;BSN-AS2增加体内肿瘤细胞增殖和肿瘤生长,miR-219a-5p则能抑制。结论:BSN-AS2竞争性结合miR-219a-5p促进NSCLC细胞侵袭、迁移和增殖,且抑制凋亡,而干扰BSN-AS2-miR-219a-5p轴可能作为抗NSCLC的新靶点。

Objective:To investigate the mechanism of BSN-AS2 competitively binding miR-219a-5p regulating the proliferation,migration,invasion and apoptosis of NSCLC cells.Methods:Expression of BSN-AS2 and miR-219a-5p in NSCLC tissues and cell lines was detected by using quantitative real time polymerase chain reaction(qRT-PCR).The signal intensity of BSN-AS2 and miR-219a-5p was detected by using fluorescence in situ hybridization(FISH).Double-luciferase reporter gene assay was used to verify that miR-219a-5p targeted and regulated BSN-AS2.Transwell,CCK8 and Tunel were used to respectively detect effect of BSN-AS2-miR-219a-5p axis on cell invasion,migration,proliferation and apoptosis.The xenograft model of NSCLC in nude mice was constructed to verify the regulatory role of BSN-AS2-miR-219a-5p axis.Results:BSN-AS2 showed a high expression in NSCLC tissues and cell lines,whereas miR-219a-5p was low expressed,and BSN-AS2 competitively bound to miR-219a-5p.siBSN-AS2 inhibited the invasion,migration and proliferation of NCI-H520 cells and promoted apoptosis.The In-miR-219a-5p group promoted NCI-H520 cell invasion,migration and proliferation and inhibited cell apoptosis.siBSN-AS2+In-miR-219a-5p group promoted NCI-H520 cell invasion,migration and proliferation,and inhibited cell apoptosis compared with siBSN-AS2 group.BSN-AS2 enhanced tumor cell proliferation and tumor growth in vivo,while miR-219a-5p exerted inhibitory function.Conclusion:BSN-AS2 competitively binds to miR-219a-5p to facilitate NSCLC cell invasion,migration and proliferation,and inhibits apoptosis,while siBSN-AS2-miR-219a-5p axis can be a novel target of anti-NSCLC.