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TRG-AS1 通过 microRNA-543/Yes 相关蛋白 1 轴调控促进舌鳞状细胞癌的致癌性。

TRG-AS1 is a potent driver of oncogenicity of tongue squamous cell carcinoma through microRNA-543/Yes-associated protein 1 axis regulation.

机构信息

Department of Nuclear Medicine, The First Affiliated Hospital of Zhengzhou University , Zhengzhou, Henan, P.R. China.

出版信息

Cell Cycle. 2020 Aug;19(15):1969-1982. doi: 10.1080/15384101.2020.1786622. Epub 2020 Jul 2.

DOI:10.1080/15384101.2020.1786622
PMID:32615889
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7469544/
Abstract

The long noncoding RNA T cell receptor gamma locus antisense RNA 1 (TRG-AS1) plays an important role in glioblastoma progression. The objective of this study was to determine the expression status of TRG-AS1 in tongue squamous cell carcinoma (TSCC). The regulatory effects of TRG-AS1 depletion on the malignant processes of TSCC cells were illustrated both and . Additionally, the precise molecular mechanisms through which TRG-AS promotes TSCC oncogenicity were investigated. TRG-AS1 expression in TSCC tissues and cell lines was detected using reverse transcription-quantitative PCR. Functional experiments including Cell Counting Kit-8 assay, flow cytometric apoptotic assay, migration and invasion assays, and xenograft tumor model analysis were conducted to severally determine the effects of TRG-AS1 on TSCC cell proliferation, apoptosis, migration, and invasion and tumor growth . Herein, TRG-AS1 was highly expressed in TSCC and closely associated with advanced TNM stage, high lymph node metastasis, and poor overall survival. Functionally, TRG-AS1 depletion suppressed TSCC cell proliferation, migration, and invasion ; promoted cell apoptosis; and attenuated tumor growth . Mechanistically, TRG-AS1 served as a molecular sponge for microRNA-543 (miR-543), thereby contributing to the increased expression of Yes-associated protein 1 (YAP1) - a miR-543 target. Rescue experiments confirmed that miR-543 inhibition or YAP1 overexpression abrogated the anticancer effects of TRG-AS1 silencing in TSCC cells. In conclusion, TRG-AS1 aggravates TSCC malignancy by regulating the miR-543/YAP1 axis. Identification of the TRG-AS1/miR-543/YAP1 regulatory pathway may provide novel insights into TSCC diagnosis, prognosis, and therapy.

摘要

长链非编码 RNA 受体γ基因座反义 RNA1(TRG-AS1)在胶质母细胞瘤的进展中起着重要作用。本研究旨在确定 TRG-AS1 在舌鳞癌(TSCC)中的表达状态。通过体外和体内实验阐明了 TRG-AS1 耗竭对 TSCC 细胞恶性进程的调节作用。此外,还研究了 TRG-AS 促进 TSCC 致癌性的确切分子机制。采用逆转录定量 PCR 检测 TSCC 组织和细胞系中 TRG-AS1 的表达。通过细胞计数试剂盒-8 测定、流式细胞术凋亡测定、迁移和侵袭测定以及异种移植肿瘤模型分析等功能实验,分别确定 TRG-AS1 对 TSCC 细胞增殖、凋亡、迁移和侵袭以及肿瘤生长的影响。在此,TRG-AS1 在 TSCC 中高表达,与晚期 TNM 分期、高淋巴结转移和不良总生存期密切相关。功能上,TRG-AS1 耗竭抑制 TSCC 细胞增殖、迁移和侵袭;促进细胞凋亡;并减弱肿瘤生长。机制上,TRG-AS1 作为 microRNA-543(miR-543)的分子海绵,从而导致 Yes 相关蛋白 1(YAP1)的表达增加 - miR-543 的靶标。挽救实验证实,miR-543 抑制或 YAP1 过表达可消除 TRG-AS1 沉默对 TSCC 细胞的抗癌作用。总之,TRG-AS1 通过调节 miR-543/YAP1 轴加重 TSCC 恶性程度。鉴定 TRG-AS1/miR-543/YAP1 调控通路可能为 TSCC 的诊断、预后和治疗提供新的见解。

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