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玉竹凝集素通过调控人肺腺癌A549细胞中的微小RNA-1290和微小RNA-15a-3p诱导细胞凋亡和自噬。

Polygonatum odoratum lectin induces apoptosis and autophagy by regulation of microRNA-1290 and microRNA-15a-3p in human lung adenocarcinoma A549 cells.

作者信息

Wu Lei, Liu Tao, Xiao Yan, Li Xin, Zhu Yanan, Zhao Yan, Bao Jinku, Wu Chuanfang

机构信息

School of Life Sciences and Key Laboratory of Bio-resources and Eco-environment, Ministry of Education, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu 610064, China.

School of Life Sciences and Key Laboratory of Bio-resources and Eco-environment, Ministry of Education, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu 610064, China.

出版信息

Int J Biol Macromol. 2016 Apr;85:217-26. doi: 10.1016/j.ijbiomac.2015.11.014. Epub 2015 Nov 10.

Abstract

Polygonatum odoratum lectin (POL), a mannose-binding specific Galanthus nivalis agglutinin (GNA)-related lectin has been reported with remarkable anti-proliferative and apoptosis-inducing effects against several tumor cells. Our previous research revealed that POL can induce apoptosis and autophagy in A549 cells. However, whether microRNAs (miRNAs) are involved in POL-induced apoptosis and autophagy in A549 cells has not been investigated. The aim of this study was to evaluate whether miRNAs were involved in POL-induced apoptosis and autophagy in A549 cells. In the present study, we performed microarray analysis on A549 cells to identify altered miRNAs after POL treatment. We found that miR-1290 was down-regulated after POL treatment and down-regulated miR-1290 amplifies POL-induced apoptosis in A549 cells. Moreover, we revealed that glycogen synthase kinase-3β (GSK3β) was a direct target of miR-1290 and POL treatment could result in Wnt pathway down regulation. We also found that miR-15a-3p was up-regulated after POL treatment and over-expression of miR-15a-3p resulted in A549 cells apoptosis and autophagy. In addition, we confirmed that a miR-15a-3p mediated ROS-p53 pathway was involved in POL-induced apoptosis and autophagy in A549 cells. Taken together, these data provide evidence that POL induces A549 cells apoptosis and autophagy by regulation of miR-1290 and miR-15a-3p.

摘要

玉竹凝集素(POL)是一种与甘露糖结合特异性的雪花莲凝集素(GNA)相关的凝集素,据报道它对多种肿瘤细胞具有显著的抗增殖和诱导凋亡作用。我们之前的研究表明,POL可诱导A549细胞凋亡和自噬。然而,微小RNA(miRNA)是否参与POL诱导的A549细胞凋亡和自噬尚未见研究报道。本研究的目的是评估miRNA是否参与POL诱导的A549细胞凋亡和自噬。在本研究中,我们对A549细胞进行了微阵列分析,以鉴定POL处理后miRNA的变化。我们发现POL处理后miR-1290表达下调,而下调的miR-1290可增强POL诱导的A549细胞凋亡。此外,我们发现糖原合酶激酶-3β(GSK3β)是miR-1290的直接靶点,POL处理可导致Wnt信号通路下调。我们还发现POL处理后miR-15a-3p表达上调,miR-15a-3p过表达可导致A549细胞凋亡和自噬。此外,我们证实miR-15a-3p介导的ROS-p53信号通路参与了POL诱导的A549细胞凋亡和自噬。综上所述,这些数据表明POL通过调节miR-1290和miR-15a-3p诱导A549细胞凋亡和自噬。

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