环状 RNA 抑制肺腺癌的进展通过调节 miR-6783-3p/DKK1 轴和失活 Wnt/β-连环蛋白信号通路。
CircRNA has_circ_0006427 suppresses the progression of lung adenocarcinoma by regulating miR-6783-3p/DKK1 axis and inactivating Wnt/β-catenin signaling pathway.
机构信息
Department of Thoracic Surgery, Ningbo No.2 Hospital, No.41 Northwest Street, Ningbo City, Zhejiang Province, 315010, China.
Department of Thoracic Surgery, Ningbo No.2 Hospital, No.41 Northwest Street, Ningbo City, Zhejiang Province, 315010, China.
出版信息
Biochem Biophys Res Commun. 2019 Jan 1;508(1):37-45. doi: 10.1016/j.bbrc.2018.11.079. Epub 2018 Nov 20.
Recently, circular RNAs (circRNAs) are identified as a novel class of noncoding RNAs playing important roles in human malignant tumors. However, the regulatory function of circRNA in lung adenocarcinoma (LUAD) is still largely unknown. Present study aimed to explore the role of circ_0006427 in LUAD progression. Firstly, the downregulation of circ_0006427 in LUAD tissues and cell lines was revealed by microarray analysis and qRT-PCR analysis. And we also confirmed the circ_0006427 as a prognostic target in LUAD patients. Functionally, overexpression of circ_0006427 effectively suppressed cell proliferation, migration and invasion. Mechanistically, circ_0006427 was found to be predominantly located in the cytoplasm of LUCA cell, and was further revealed to positively regulate DKK1 in LUAD by sponging miR-6783-3p. KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analysis and western blot analysis revealed that circ_0006427 inactivated Wnt/β-catenin signaling pathway by upregulating DKK1. At last, rescue assays proved the function of circ_0006427/miR-6783-3p/DKK1 axis in LUAD progression. In conclusion, our study revealed that circ_0006427 suppressed lung adenocarcinoma progression through regulating miR-6783-3p/DKK1 axis.
最近，环状 RNA（circRNA）被鉴定为一类新型的非编码 RNA，在人类恶性肿瘤中发挥重要作用。然而，circRNA 在肺腺癌（LUAD）中的调控功能在很大程度上仍然未知。本研究旨在探讨 circ_0006427 在 LUAD 进展中的作用。首先，通过微阵列分析和 qRT-PCR 分析揭示了 circ_0006427 在 LUAD 组织和细胞系中的下调。并且我们还证实了 circ_0006427 是 LUAD 患者的一个预后靶点。功能上，circ_0006427 的过表达有效抑制了细胞增殖、迁移和侵袭。机制上，发现 circ_0006427 主要位于 LUCA 细胞的细胞质中，并通过海绵吸附 miR-6783-3p 正向调节 LUAD 中的 DKK1。KEGG（京都基因与基因组百科全书）通路分析和 Western blot 分析表明，circ_0006427 通过上调 DKK1 使 Wnt/β-catenin 信号通路失活。最后，挽救实验证明了 circ_0006427/miR-6783-3p/DKK1 轴在 LUAD 进展中的功能。总之，我们的研究表明，circ_0006427 通过调节 miR-6783-3p/DKK1 轴抑制肺腺癌的进展。
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