MiR-532-3p抑制弥漫性大B细胞淋巴瘤细胞增殖的机制研究

Mechanism Underlying the Inhibitory Effect of MiR-532-3p on the Cells Proliferation of Diffuse Large B-Cell Lymphoma

目的:研究miR-532-3p和脂蟾毒甙元(RES)通过调节Wnt/β-catenin信号对弥漫性大B细胞淋巴瘤(DLBCL)细胞活性的作用机制。方法:收集2019年10月至2021年10月兰州市兰州大学第一医院DLBCL患者的癌组织样本及癌旁组织样本;将SU-DHL-4细胞分为mimics-NC组、miR-532-3pmimics组及对照组、脂蟾毒甙元组(RES组)。采用RT-qPCR法检测miR-532-3p的表达水平;Western blot检测β-catenin的蛋白含量;MTT法检测SUDHL-4细胞的增殖活性。结果:相比于癌旁淋巴组织,淋巴癌组织中的miR-532-3p表达明显降低(P<0.001);淋巴瘤细胞中的miR-532-3p的含量显著低于正常淋巴细胞(P<0.001)。过表达miR-532-3p后,SU-DHL-4细胞的增殖活性明显下降(P<0.01),而β-catenin的表达亦显著减少(P<0.05)。相比于对照组,RES抑制了SU-DHL-4细胞的增殖,同时降低了细胞中β-catenin的表达。结论:过表达miR-532-3p降低Wnt/β-catenin信号,并抑制淋巴瘤细胞的增殖;RES可通过抑制Wnt/β-catenin的表达,降低淋巴瘤细胞的增殖活性。

Objective:To investigate the effects and underlying mechanism of miR-532-3p and resibufogenin(RES)by regulating Wnt/β-catenin signaling on diffuse Large B-cell lymphoma(DLBCL)cells proliferation. Methods:DLBCL tissues and adjacent normal tissues were collected from patients had been diagnosed with DLBCL at the First Hospital of Lanzhou University from October2019to October2021. Four groups including mimics-NC,miR-532-3p mimics,RES control and RES treatment in SU-DHL-4cells were designed. The expression level of miR-532-3p was detected by RT-qPCR. The protein content ofβ-catenin was detected by Western blot. MTT assay was used to detect the proliferation activity of SU-DHL-4cells. Results:miR-532-3p expression was significantly decreased in DLBCL tissues compared with adjacent normal tissues(P< 0.001). The miR-532-3p content in lymphoma cells was significantly lower than that in normal lymphocytes(P< 0.001). After overexpression of miR-532-3p,the viability of SU-DHL4cells was significantly decreased(P< 0.001),with a reduced expression ofβ-catenin(P< 0.05). RES treatment inhibited the proliferation of SU-DHL-4cells and decreasedβ-catenin expression in SU-DHL-4cells compared with the control group.Conclusion:Overexpression of miR-532-3p reduced Wnt/β-catenin signaling and inhibited the proliferation of lymphoma cells. Moreover,RES treatment inhibited lymphoma cells growth partially through Wnt/β-catenin signaling suppression.