首页|lncRNA MALAT1通过海绵吸附miRNA-141-3p调控Wnt/β-catenin促进卵巢癌的生长及转移

lncRNA MALAT1通过海绵吸附miRNA-141-3p调控Wnt/β-catenin促进卵巢癌的生长及转移

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目的 研究长链非编码 RNA MALAT1(lncRNA MALAT1)在卵巢癌中的作用及调控机制.方法 实时荧光定量聚合酶链反应(real-time quantitative polymerase chain reaction,RT-qPCR)检测 MALAT1 在人正常卵巢上皮细胞系 IOSE80 及人卵巢癌细胞系SKOV3、OVCA429 和HO-8910PM 中的表达,选取SKOV3 及HO-8910PM 细胞进行后续研究.利用siRNA干扰SK-OV3 和 HO-8910PM 细胞中 MALAT1 表达,CCK-8 法检测细胞增殖,划痕及 Transwell 小室检测细胞迁移及侵袭能力,并通过Western blot法检测上皮-间充质转化(epithelial-mesenchymal transformation,EMT)相关指标 E-cadherin、N-cadherin的表达.利用生物信息学分析 MALAT1 与 miRNA-141-3p 的靶向关系,并利用双荧光素报告基因验证.MALAT1 敲低及 miRNA-141-3p抑制剂共同作用细胞,检测其对 SKOV3 及 HO-8910PM 细胞增殖、侵袭及迁移的影响,并通过 Western blot法分析其对Wnt/β-catenin信号通路相关蛋白的表达调控.结果 与人正常卵巢上皮细胞系 IOSE80 比较,卵巢癌细胞系内 MALAT1 表达明显上调(P<0.05);而在SKOV3 及HO-8910PM 中下调MALAT1 表达,细胞增殖、侵袭迁移及EMT均受到抑制,同时miRNA-141-3p表达上调(P<0.05).双荧光素酶报告基因结果证明 MALAT1 和 miRNA-141-3p具有靶向关系.而在下调 MALAT1表达的同时使用 miRNA-141-3p抑制剂,则可逆转下调 MALAT1 的所产生的抑制效应(P<0.05).进一步的研究发现,MAL-AT1/miRNA-141-3p轴可能通过调控 Wnt/β-catenin信号通路影响卵巢癌进展.结论 MALAT1 可能通过海绵吸附miRNA-141-3 从而调控 Wnt/β-catenin影响卵巢癌的发生和发展.
lncRNA MALAT1 Regulates Wnt/β-catenin by Sponge Adsorption of MiRNA-141-3p to Promote the Growth and Metastasis of Ovarian Cancer
Objective To study the role and regulatory mechanism of long non-coding RNA MALAT1 in ovarian cancer.Methods Real-time quantitative polymerase chain reaction(RT-qPCR)was used to detect the expression of MALAT1 in human normal ovarian epithelial cell line IOSE80 and human ovarian cancer cell line SKOV3,OVCA429 and HO-8910PM.SKOV3 and HO-8910PM cells were selected for the next study.The expression of MALAT1 in SKOV3 and HO-8910PM cells were interfered with siRNA,the cell pro-liferation was detectd by CCK-8 method,the cell migration and invasion were detectd by scratche and Transwell assay respectively,and the expression of epithelial-mesenchymal transformation(EMT)-related indicators E-cadherin and N-cadherin were detected by Western blot.The targeting relationship between MALAT1 and miRNA-141-3p was analyzed by bioinformatics,and was verified by du-al luciferase reporter.MALAT1 knockdown and miRNA-141-3p inhibitor were treated the SKOV3 and HO-8910PM cells at the same time,then the cell proliferation,invasion and migration were detected,Western blot was used to detect the expression of Wnt/β-catenin signaling pathway related proteins.Results Compared with human normal ovarian epithelial cell line IOSE80,the expression of MALAT1 in ovarian cancer cell line was significantly up-regulated(P<0.05).When the expression of MALAT1 in SKOV3 and HO-8910PM was down-regulated,the cell proliferation,invasion,migration and EMT were inhibited(P<0.05).At the same time,the expression of miRNA-141-3p was up-regulated(P<0.05),and the results of dual luciferase reporter proved that there was a targeting relation-ship between MALAT1 and miRNA-141-3p.However,the inhibitory effect of MALAT1down-regulation in the cells can be reversed by miRNA-141-3p inhibitor(P<0.05).Further studies had found that the MALAT1/miRNA-141-3p axis may influence the pro-gression of ovarian cancer by regulating the Wnt/β-catenin signaling pathway.Conclusion MALAT1may influence the occurrence and development of ovarian cancer by sponge adsorption of miRNA-141-3 via regulating Wnt/β-catenin.

Ovarian cancerLncRNA MALAT1MiRNA-141-3pWnt/β-cateninProliferation

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310006 杭州,浙江大学医学院附属妇产科医院肿瘤科

卵巢癌 lncRNA mALAT1 miRNA-141-3p Wnt/β-catenin 增殖

浙江省基础公益研究计划

LQ20H040009

2024

医学研究杂志
中国医学科学院

医学研究杂志

CSTPCD
影响因子:0.702
ISSN:1673-548X
年,卷(期):2024.53(4)
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