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ETV4 介导的长链非编码 RNA C2CD4D-AS1 过表达通过 miR-3681-3p/NEK2 轴促进肺腺癌细胞的恶性表型。

ETV4 mediated lncRNA C2CD4D-AS1 overexpression contributes to the malignant phenotype of lung adenocarcinoma cells via miR-3681-3p/NEK2 axis.

机构信息

Department of Respiratory Disease, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.

Department of Respiratory Disease, Taizhou First People's Hospital, Taizhou, Zhejiang, China.

出版信息

Cell Cycle. 2021 Dec;20(24):2607-2618. doi: 10.1080/15384101.2021.2005273. Epub 2021 Dec 1.

DOI:10.1080/15384101.2021.2005273
PMID:34850664
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8726644/
Abstract

Lung adenocarcinoma (LUAD) is originated from the mucus-producing glands of the lungs. The involvement of long noncoding RNAs (lncRNAs) has been discovered in multiple diseases. In the present research, we aimed to unmask the role of C2CD4D and THEM5 antisense RNA 1 (C2CD4D-AS1) in LUAD. RT-qPCR or western blot analysis was respectively applied in the detection of RNA or protein expressions. The function of C2CD4D-AS1 in LUAD was assessed by functional assays. Through ChIP, RNA pull down, DNA pull down, RIP and luciferase reporter assays, the in-depth regulatory mechanism of C2CD4D-AS1 in LUAD was explored. C2CD4D-AS1 was dramatically overexpressed in LUAD tissues and cell lines. As a result, depletion of C2CD4D-AS1 significantly repressed cell proliferation, migration, invasion and stimulated cell apoptosis in LUAD. Mechanistically, ETS variant transcription factor 4 (ETV4) activated the transcription of C2CD4D-AS1 and stimulated its up-regulation in LUAD cells, thus affecting LUAD cell biological functions. Furthermore, C2CD4D-AS1 sponged microRNA-3681-3p (miR-3681-3p) and regulated NIMA-related kinase 2 (NEK2), thus participating in modulating LUAD cell biological behaviors. To conclude, C2CD4D-AS1 up-regulation induced by ETV4 enhanced NEK2 expression by sequestering miR-3681-3p to contribute to the malignant behaviors of LUAD cells.

摘要

肺腺癌 (LUAD) 起源于肺部的黏液产生腺。长链非编码 RNA (lncRNA) 的参与已在多种疾病中被发现。在本研究中，我们旨在揭示 C2CD4D 和 THEM5 反义 RNA 1 (C2CD4D-AS1) 在 LUAD 中的作用。分别应用 RT-qPCR 或 Western blot 分析检测 RNA 或蛋白表达。通过功能测定评估 C2CD4D-AS1 在 LUAD 中的功能。通过 ChIP、RNA 下拉、DNA 下拉、RIP 和荧光素酶报告基因测定，探讨了 C2CD4D-AS1 在 LUAD 中的深入调控机制。C2CD4D-AS1 在 LUAD 组织和细胞系中显著过表达。结果表明，C2CD4D-AS1 的耗竭显著抑制 LUAD 细胞的增殖、迁移、侵袭，并刺激细胞凋亡。机制上，ETS 变异转录因子 4 (ETV4) 激活 C2CD4D-AS1 的转录，刺激其在 LUAD 细胞中的上调，从而影响 LUAD 细胞的生物学功能。此外，C2CD4D-AS1 海绵 microRNA-3681-3p (miR-3681-3p) 并调节丝氨酸/苏氨酸激酶 2 (NEK2)，从而参与调节 LUAD 细胞的生物学行为。总之，由 ETV4 诱导的 C2CD4D-AS1 的上调通过海绵 miR-3681-3p 增强 NEK2 的表达，从而促进 LUAD 细胞的恶性行为。

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[1]
ETV4 mediated lncRNA C2CD4D-AS1 overexpression contributes to the malignant phenotype of lung adenocarcinoma cells via miR-3681-3p/NEK2 axis.

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引用本文的文献

[1]
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Front Immunol. 2025-5-21

[2]
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Mol Med Rep. 2025-4

[3]
Role of NEK2 in tumorigenesis and tumor progression.

Trends Mol Med. 2025-1

[4]
Overview of carboxyl‑terminal modulator protein 1 and its importance in various metabolic regulations (Review).

Mol Med Rep. 2024-9

[5]
Abnormal methylation mediated upregulation of LINC00857 boosts malignant progression of lung adenocarcinoma by modulating the miR-486-5p/NEK2 axis.

Clin Respir J. 2024-5

[6]
LncRNA PCED1B-AS1 mediates miR-3681-3p/MAP2K7 axis to promote metastasis, invasion and EMT in gastric cancer.

Biol Direct. 2024-5-2

[7]
Long noncoding RNA SNHG4 promotes the malignant progression of hepatocellular carcinoma through the miR-211-5p/CREB5 axis.

Cancer Med. 2023-4

[8]
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[9]
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本文引用的文献

[1]
High expression of NEK2 promotes lung cancer progression and drug resistance and is regulated by mutant EGFR.

Mol Cell Biochem. 2020-12

[2]
ETV4 Is Necessary for Estrogen Signaling and Growth in Endometrial Cancer Cells.

Cancer Res. 2020-2-11

[3]
ETV4 overexpression promotes progression of non-small cell lung cancer by upregulating PXN and MMP1 transcriptionally.

Mol Carcinog. 2019-10-31

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Long Non-Coding RNA (lncRNA) X-Inactive Specific Transcript (XIST) Plays a Critical Role in Predicting Clinical Prognosis and Progression of Colorectal Cancer.

Med Sci Monit. 2019-8-27

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Cancer Biomark. 2019

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ETV4 promotes proliferation and invasion of lung adenocarcinoma by transcriptionally upregulating MSI2.

Biochem Biophys Res Commun. 2019-6-25

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Oncol Lett. 2019-4

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Mol Cancer. 2018-11-23

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Pathologica. 2018-3

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Integrative Analysis of lncRNAs in Th17 Cell Lineage to Discover New Potential Biomarkers and Therapeutic Targets in Autoimmune Diseases.

Mol Ther Nucleic Acids. 2018-9-7

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