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长链非编码RNA GSEC通过靶向miR-202-5p/AXL轴促进三阴性乳腺癌(TNBC)进展。

lncRNA GSEC Promotes the Progression of Triple Negative Breast Cancer (TNBC) by Targeting the miR-202-5p/AXL Axis.

作者信息

Zhang Jianhua, Du Chuang, Zhang Linfeng, Wang Yan, Zhang Yingying, Li Jingruo

机构信息

Department of Breast Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou City, Henan Province, 450000, People's Republic of China.

出版信息

Onco Targets Ther. 2021 Apr 20;14:2747-2759. doi: 10.2147/OTT.S293832. eCollection 2021.

Abstract

BACKGROUND

This study aimed to explore the biological functions of G-quadruplex-forming sequence containing lncRNA (GSEC) in triple negative breast cancer (TNBC).

METHODS

The expression of GSEC in TNBC tissues was evaluated by qRT-PCR. Cell viability was evaluated by Cell Counting Kit-8 assay. Cell proliferation was evaluated by 5-ethynyl-20-deoxyuridine (EdU) staining assay. Cell invasion and migration were evaluated by Transwell assay. Gain- and loss-function assays were performed to assess the biological functions of GSEC in TNBC. The interactions between GSEC, miR-202-5p and AXL were determined by luciferase report assay and RNA immunoprecipitation (RIP) assay. In addition, a nude mouse xenograft model was used to confirm the oncogenic role of GSEC in TNBC.

RESULTS

GSEC was significantly upregulated in TNBC tissues and cancer cell lines, and high level of GSEC was associated with advanced tumor stage, positive lymph-node metastasis and the poor prognosis of TNBC patients. Knockdown of GSEC effectively inhibited TNBC cell proliferation, invasion and migration in vitro. GSEC regulated the expression of AXL by directly sponging miR-202-5p. Downregulation of miR-202-5p attenuated GSEC knockdown-induced inhibition on TNBC cell proliferation, invasion and migration in vitro. Meanwhile, overexpression of AXL obviously reversed the inhibitory effects of miR-202-5p mimics in TNBC progression in vitro.

CONCLUSION

GSEC functioned as a potential oncogene and promoted AXL-mediated TNBC progression by sponging miR-202-5p, which might be a novel diagnostic and therapeutic target for TNBC.

摘要

背景

本研究旨在探讨含G-四链体形成序列的长链非编码RNA(GSEC)在三阴性乳腺癌(TNBC)中的生物学功能。

方法

采用qRT-PCR评估GSEC在TNBC组织中的表达。通过细胞计数试剂盒-8法评估细胞活力。采用5-乙炔基-2'-脱氧尿苷(EdU)染色法评估细胞增殖。通过Transwell法评估细胞侵袭和迁移。进行功能获得和功能缺失实验以评估GSEC在TNBC中的生物学功能。通过荧光素酶报告实验和RNA免疫沉淀(RIP)实验确定GSEC、miR-202-5p和AXL之间的相互作用。此外,使用裸鼠异种移植模型来证实GSEC在TNBC中的致癌作用。

结果

GSEC在TNBC组织和癌细胞系中显著上调,高水平的GSEC与肿瘤晚期、阳性淋巴结转移以及TNBC患者的不良预后相关。敲低GSEC可有效抑制TNBC细胞在体外的增殖、侵袭和迁移。GSEC通过直接结合miR-202-5p来调节AXL的表达。下调miR-202-5p可减弱GSEC敲低诱导的对TNBC细胞在体外增殖、侵袭和迁移的抑制作用。同时,过表达AXL明显逆转了miR-202-5p模拟物对TNBC体外进展的抑制作用。

结论

GSEC作为一种潜在的癌基因,通过结合miR-202-5p促进AXL介导的TNBC进展,这可能是TNBC的一个新的诊断和治疗靶点。

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