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长链非编码 RNA TDRG1 通过靶向 miR-214-5p/CLIC4 轴促进乳腺癌细胞增殖、迁移和侵袭。

Long non-coding RNA TDRG1 facilitates cell proliferation, migration and invasion in breast cancer via targeting miR-214-5p/CLIC4 axis.

机构信息

Department of General Surgery, Qilu Hospital of Shandong University, Jinan, 250012, Shandong, China.

Department of General Surgery, Qilu Hospital of Shandong University (Qingdao Branch), Qingdao, 266000, Shandong, China.

出版信息

Cancer Biol Ther. 2021 Mar 4;22(3):248-256. doi: 10.1080/15384047.2020.1863120. Epub 2021 Apr 6.

DOI:10.1080/15384047.2020.1863120
PMID:33822672
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8043166/
Abstract

Accumulated studies have revealed the critical role of long non-coding RNAs (lncRNAs) in the carcinogenesis and progression of various cancers. LncRNA TDRG1 has been reported to exhibit oncogenic potential in some cancers. However, its underlying mechanism regulating breast cancer (BC) remains obscure. QRT-PCR was used to measure the relative expression of mRNAs, and western blot was used to detect protein expression levels. CCK8 and CFSE assays were utilized to testify cell proliferation ability. Flow cytometry assay was used for cell apoptosis ability investigation. Transwell and tube formation assays were implemented to test cell migrating and invasive abilities. Relevant mechanism experiments were implemented to determine the molecular mechanism. TDRG1 was remarkably overexpressed in BC cell lines. TDRG1 knockdown suppressed cell proliferation, migration and invasion, but enhanced BC cell apoptosis. Mechanistically, TDRG1 acted as a miR-214-5p sponge to up-regulate CLIC4 expression. MiR-214-5p inhibition or CLIC4 overexpression could revive the tumor-suppressing effects induced by TDRG1 knockdown. TDRG1 promoted cell proliferation, migration, and invasion in BC, suggesting that TDRG1 could promisingly be a therapeutic target for BC.

摘要

已有研究揭示长链非编码 RNA(lncRNA)在多种癌症的发生和发展中起着关键作用。有研究报道 lncRNA TDRG1 在一些癌症中具有致癌潜能。然而,其调节乳腺癌(BC)的潜在机制尚不清楚。实时定量 PCR(QRT-PCR)用于测量 mRNA 的相对表达水平,Western blot 用于检测蛋白表达水平。CCK8 和 CFSE 实验用于检测细胞增殖能力。流式细胞术用于检测细胞凋亡能力。Transwell 和管形成实验用于检测细胞迁移和侵袭能力。实施相关机制实验以确定分子机制。TDRG1 在 BC 细胞系中显著过表达。TDRG1 敲低抑制细胞增殖、迁移和侵袭,但增强 BC 细胞凋亡。机制上,TDRG1 作为 miR-214-5p 的海绵体,上调 CLIC4 的表达。miR-214-5p 抑制或 CLIC4 过表达可以恢复 TDRG1 敲低诱导的肿瘤抑制作用。TDRG1 促进 BC 中的细胞增殖、迁移和侵袭,表明 TDRG1 可能是 BC 的有前途的治疗靶点。

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