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长链非编码 RNA TDRG1 通过海绵吸附 miR-214-5p 靶向 SOX4 促进宫颈癌细胞的增殖、迁移和侵袭。

LncRNA TDRG1 promotes the proliferation, migration, and invasion of cervical cancer cells by sponging miR-214-5p to target SOX4.

机构信息

Department of Gynecology, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.

Shaoxing Women and Children's Hospital, Shaoxing, Zhejiang, China.

出版信息

J Recept Signal Transduct Res. 2020 Jun;40(3):281-293. doi: 10.1080/10799893.2020.1731537. Epub 2020 Feb 27.

Abstract

The pathogenesis of cervical cancer (CC) at molecular level has attracted much research attention. The current study aimed to explore the effects of LncRNA TDRG1 on cellular process in CC cells and its molecular mechanism. Expressions of TDRG1 and miR-214-5p in CC and normal tissues and CC cells were measured by quantitative real-time polymerase chain reaction (qRT-PCR). The effects of TDRG1, miR-214-5p, and SOX4 on cell proliferation, migration, invasion, and EMT process of CC cells were detected by Cell Counting Kit-8 (CCK-8), colony formation, wound-healing, Transwell, and Western blot assays, respectively. StarBase and Targetscan7.2 were used to predict the target genes of TDRG1 and miR-214-5p, and the predictions were verified by dual-luciferase reporter assay. The expression of SOX4 in CC and normal tissues, and CC cells transfected with siTDRG1 or miR-214-5p inhibitor was determined by qRT-PCR. The results showed that expression of TDRG1 was up-regulated, while that of miR-214-5p was down-regulated in CC. The target genes of TDRG1 and miR-214-5p were verified to be miR-214-5p and SOX4, respectively. Knocking down TDRG1 expression could inhibit cell proliferation, colony, migration, and invasion abilities, and EMT process, whereas the inhibition of miR-214-5p expression partially reversed such results. Moreover, high SOX4 expression was observed in CC tissues, and down-regulating TDRG1 expression reduced the SOX4 expression while down-regulating miR-214-5p expression alleviated such an inhibition. In conclusion, TDRG1 acts as cancer promoter in CC through promoting cell proliferation, migration, invasion, and EMT process to modulate SOX4 expression through adsorbing miR-214-5p.

摘要

宫颈癌(CC)在分子水平上的发病机制引起了广泛的研究关注。本研究旨在探讨 LncRNA TDRG1 对 CC 细胞中细胞过程的影响及其分子机制。通过实时定量聚合酶链反应(qRT-PCR)测量 CC 和正常组织以及 CC 细胞中 TDRG1 和 miR-214-5p 的表达。通过细胞计数试剂盒-8(CCK-8)、集落形成、划痕愈合、Transwell 和 Western blot 测定分别检测 TDRG1、miR-214-5p 和 SOX4 对 CC 细胞增殖、迁移、侵袭和 EMT 过程的影响。使用 StarBase 和 Targetscan7.2 预测 TDRG1 和 miR-214-5p 的靶基因,并通过双荧光素酶报告基因实验验证预测结果。通过 qRT-PCR 测定 CC 和正常组织以及转染 siTDRG1 或 miR-214-5p 抑制剂的 CC 细胞中 SOX4 的表达。结果显示,CC 中 TDRG1 的表达上调,而 miR-214-5p 的表达下调。验证了 TDRG1 和 miR-214-5p 的靶基因分别是 miR-214-5p 和 SOX4。敲低 TDRG1 表达可抑制细胞增殖、集落形成、迁移和侵袭能力以及 EMT 过程,而抑制 miR-214-5p 表达部分逆转了这种结果。此外,在 CC 组织中观察到 SOX4 高表达,下调 TDRG1 表达可降低 SOX4 表达,而下调 miR-214-5p 表达可减轻这种抑制作用。总之,TDRG1 通过吸附 miR-214-5p 来调节 SOX4 表达,从而在 CC 中作为癌基因促进细胞增殖、迁移、侵袭和 EMT 过程。

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