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长链非编码 RNA LINC01006 通过靶向 microRNA 129-2-3p/CTNNB1 轴并激活 Wnt/β-连环蛋白信号通路促进肺腺癌细胞增殖、迁移和上皮-间充质转化。

Long Noncoding RNA LINC01006 Facilitates Cell Proliferation, Migration, and Epithelial-Mesenchymal Transition in Lung Adenocarcinoma via Targeting the MicroRNA 129-2-3p/CTNNB1 Axis and Activating Wnt/β-Catenin Signaling Pathway.

机构信息

Department of Lung Cancer, Tianjin Medical University Cancer Institute & Hospital, Tianjin, China.

出版信息

Mol Cell Biol. 2021 May 21;41(6):e0038020. doi: 10.1128/MCB.00380-20.

Abstract

Lung adenocarcinoma (LUAD) is a common type of malignancy of lung cancers. Long intergenic noncoding RNAs (lincRNAs) have emerged as crucial regulators of various cancers, including LUAD. LINC01006 is a newly discovered long noncoding RNA (lncRNA) whose function in LUAD remains to be explored. This study is to explore the role of LINC01006 in LUAD. Quantitative real-time PCR (RT-qPCR) analysis and Western blotting were used to determine the expression levels and protein levels, respectively. Functional assays and animal experiments investigated the role of LINC01006 both and . Moreover, TOP/FOP assay was performed to detect the activation of the Wnt/β-catenin signaling pathway. The interaction between LINC01006 and microRNA 29-2-3-p (miR-29-2-3-p)/catenin beta 1 (CTNNB1) was explored by RNA binding protein immunoprecipitation (RIP), RNA pulldown, luciferase reporter assays, and rescue experiments. According to the results, LINC01006 was highly expressed in LUAD tissues and cell lines. LINC01006 knockdown significantly suppressed cell proliferative, migratory, and epithelial-mesenchymal transition (EMT) capacities and tumor development. Moreover, LINC01006 enhanced CTNNB1 via sequestering miR-129-2-3p and activated the Wnt/β-catenin pathway in LUAD. Overall, LINC01006 promotes LUAD development via activating the Wnt/β-catenin pathway, implying that LINC01006 might be a promising biomarker for LUAD treatment.

摘要

肺腺癌 (LUAD) 是肺癌的一种常见恶性肿瘤。长链非编码 RNA (lncRNA) 已成为包括 LUAD 在内的多种癌症的重要调控因子。LINC01006 是一种新发现的长非编码 RNA (lncRNA),其在 LUAD 中的功能仍有待探索。本研究旨在探讨 LINC01006 在 LUAD 中的作用。采用定量实时 PCR (RT-qPCR) 分析和 Western blot 分别测定其表达水平和蛋白水平。功能测定和动物实验研究了 LINC01006 在 LUAD 中的作用。此外,还进行了 TOP/FOP 测定以检测 Wnt/β-catenin 信号通路的激活。通过 RNA 结合蛋白免疫沉淀 (RIP)、RNA 下拉、荧光素酶报告基因测定和挽救实验探讨了 LINC01006 与 microRNA 29-2-3-p (miR-29-2-3-p)/catenin beta 1 (CTNNB1) 之间的相互作用。结果显示,LINC01006 在 LUAD 组织和细胞系中高表达。LINC01006 敲低显著抑制细胞增殖、迁移和上皮-间充质转化 (EMT) 能力以及肿瘤发展。此外,LINC01006 通过结合 miR-129-2-3p 增强 CTNNB1 并激活 LUAD 中的 Wnt/β-catenin 通路。总之,LINC01006 通过激活 Wnt/β-catenin 通路促进 LUAD 的发展,表明 LINC01006 可能成为 LUAD 治疗的有前途的生物标志物。

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