lncRNA-CASC2/miR-155-5p/APC分子轴调控非霍奇金淋巴瘤发展进程的分子机制

The Molecular Mechanism of LncRNA-CASC2/miR-155-5p/APC Axis Regulating the Progression of Non-Hodgkin Lymphoma

目的:探讨lncRNA-CASC2(CASC2)/miR-155-5p/APC分子轴对非霍奇金淋巴瘤(non-Hodgikn lymphoma,NHL)发展进程的影响。方法:qRT-PCR检测CASC2和miR-155-5p在NHL细胞系中的表达;双荧光素酶基因报告验证miR-155-5p与CASC2和APC之间的靶向关系;MTT、Transwell和流式细胞术检测CASC2/miR-155-5p/APC分子轴对NK-92细胞增殖、侵袭和凋亡的影响。结果:CASC2在NHL细胞系中低表达,过表达CASC显著抑制NK-92细胞增殖和侵袭,促进NK-92细胞凋亡;双荧光素酶基因报告验证显示miR-155-5p与CASC2和APC之间均具有靶向关系;回复实验证实,同时敲降miR-155-5p和CASC2或APC能够恢复敲降miR-155-5p对NK-92细胞生物学行为的抑制作用。结论:过表达CASC2能够抑制NK-92细胞增殖、侵袭和诱导凋亡,其机制可能是通过靶向miR-155-5p,上调APC的表达。

Objective:To investigate the effect of lncRNA-CASC2(CASC2)/miR-155-5p/APC axis to the progression of non-Hodgikn lymphoma(NHL).Methods:The expression level of CASC2 and miR-155-5p in NHL cell lines were examined by qRT-PCR.Dual-luciferase reporter gene assay was used to verify the relationship between miR-155-5p,CASC2 and APC.The effects of CASC/miR-155-5p/APC axis to the proliferation,invasion and apoptosis of NK-92 cells were detected by MTT,Transwell assay and flow cytometry assay,respectively.Results:CASC2 was downregulated in NHL cell lines.Overexpression of CASC2 could inhibit the proliferation and invasion of NK-92 cells,and promote its apoptosis.Dual-luciferase reporter gene assay confirmed that there was a targeting relationship between miR-155-5p,CASC2 and APC.The restoration experiments proved that knockdown of both miR-155-5p and CASC2 or APC could restore the inhibitory effect of miR-155-5p silencing to the biological behavior of NK-92 cells.Conclusion:Overexpression of CASC2 suppresses the proliferation and invasion of NK-92 cells,promote the apoptosis of NK-92 cells via targeting miR-155-5p and upregulating APC expression.