LncRNA TCTN2通过调控mIR-1285-3p/ARF6轴促进肝细胞癌恶性发展

IF 2.5 4区 医学 Q3 ONCOLOGY
Qian Liu, Chunfu Zhu, Yanfen Dong
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引用次数: 0

摘要

背景:肝细胞癌(HCC)是最危及生命的恶性疾病之一。TCTN2蛋白参与肿瘤的发生和发展。然而,lncRNA TCTN2是否与HCC发病机制相关尚不清楚。方法:采用实时荧光定量PCR (qRT-PCR)检测肝癌组织和细胞中lncRNA、TCTN2、miR-1285-3p、ARF6的表达。将lncRNA - tctn2特异性shRNA转染到HCC细胞中,并进行功能研究。通过双荧光素酶报告基因实验验证lncRNA TCTN2与miR-1285-3p和ARF6之间的直接相互作用。我们进行了一项救援实验来证实miR- 1285-3p/ARF6与lncRNA TCTN2相关的作用。结果:LncRNA TCTN2在HCC肿瘤组织和细胞系中高表达。lncRNA TCTN2的敲低通过调控Cyclin D1/p21和Bax/Bcl-2信号抑制细胞增殖,诱导细胞周期阻滞和凋亡。同时,lncRNA TCTN2的下调通过上调MMP2/MMP9抑制HCC细胞的迁移和侵袭。机制研究表明,lncRNA TCTN2通过海绵作用miR-1285-3p上调ARF6的表达。抢救实验表明,miR-1285-3p抑制剂逆转了lncRNA TCTN2的抗肿瘤作用,敲低ARF6抑制了HCC的进展。结论:我们的研究结果表明,lncRNA TCTN2的下调通过调节miR-1285-3p/ARF6轴抑制HCC的发展,这意味着lncRNA TCTN2在HCC中上调,可能作为HCC的诊断生物标志物。此外,它可能对HCC患者的临床治疗具有重要价值。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
LncRNA TCTN2 Promotes the Malignant Development of Hepatocellular Carcinoma via Regulating mIR-1285-3p/ARF6 Axis.

Background: Hepatocellular carcinoma (HCC) is one of the most life-threatening malignant diseases. TCTN2 protein participates in tumorigenesis and development. However, whether lncRNA TCTN2 is associated with HCC pathogenesis remains unclear.

Methods: The expression of lncRNA, TCTN2, miR-1285-3p, and ARF6 in HCC tissues and cells was detected by a quantitative Real-Time PCR (qRT-PCR) assay. lncRNA TCTN2-specific shRNA was transfected into HCC cells, and a functional investigation was performed. The direct interactions between lncRNA TCTN2 and miR-1285-3p and ARF6 were verified by dualluciferase reporter gene assay. A rescue experiment was performed to confirm the role of miR- 1285-3p/ARF6 in association with lncRNA TCTN2.

Results: LncRNA TCTN2 exhibited a high expression in HCC tumor tissues and cell lines. Knockdown of lncRNA TCTN2 suppressed cell proliferation and induced cell cycle arrest and apoptosis through regulating Cyclin D1/p21 and Bax/Bcl-2 signals. Meanwhile, the knockdown of lncRNA TCTN2 inhibited HCC cell migration and invasion through upregulating MMP2/MMP9. Mechanistic investigation revealed that lncRNA TCTN2 upregulated the expression of ARF6 via sponging miR-1285-3p. Rescue experiments indicated that miR-1285-3p inhibitor reversed the antitumor effects of lncRNA TCTN2 and ARF6 knockdown inhibited the progression of HCC.

Conclusion: Our results suggested that the knockdown of lncRNA TCTN2 inhibited HCC development by regulating the miR-1285-3p/ARF6 axis, implying that the lncRNA TCTN2 is upregulated in HCC and may serve as a diagnostic biomarker in HCC. Furthermore, it may demonstrate an important value for the clinical treatment of patients with HCC.

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来源期刊
CiteScore
4.50
自引率
7.10%
发文量
55
审稿时长
3 months
期刊介绍: Aims & Scope Recent Patents on Anti-Cancer Drug Discovery publishes review and research articles that reflect or deal with studies in relation to a patent, application of reported patents in a study, discussion of comparison of results regarding application of a given patent, etc., and also guest edited thematic issues on recent patents in the field of anti-cancer drug discovery e.g. on novel bioactive compounds, analogs, targets & predictive biomarkers & drug efficacy biomarkers. The journal also publishes book reviews of eBooks and books on anti-cancer drug discovery. A selection of important and recent patents on anti-cancer drug discovery is also included in the journal. The journal is essential reading for all researchers involved in anti-cancer drug design and discovery. The journal also covers recent research (where patents have been registered) in fast emerging therapeutic areas/targets & therapeutic agents related to anti-cancer drug discovery.
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