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长链非编码 RNA TTN-AS1 通过海绵吸附 miR-142-5p 调控 CDK5 促进肺腺癌迁移、侵袭和上皮间质转化。

LncRNA TTN-AS1 promotes migration, invasion, and epithelial mesenchymal transition of lung adenocarcinoma via sponging miR-142-5p to regulate CDK5.

机构信息

Department of Tumor Immunotherapy, Fourth Hospital of Hebei Medical University and Hebei Cancer Institute, Shijiazhuang, 050035, Hebei, China.

出版信息

Cell Death Dis. 2019 Jul 30;10(8):573. doi: 10.1038/s41419-019-1811-y.

DOI:10.1038/s41419-019-1811-y
PMID:31363080
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6667499/
Abstract

Emerging evidence suggests that long noncoding RNA (lncRNA) plays pivotal roles in regulating various biological process in human cancers. Titin-antisense RNA1 (TTN-AS1) has been regarded as a tumor promoting lncRNA in numerous cancers. However, the clinical significance and biological function of TTN-AS1 in lung adenocarcinoma (LUAD) remain unclear. In the present study, we revealed that the expression of TTN-AS1 was upregulated in LUAD tissues and cell lines. High TTN-AS1 expression was associated with TNM stage and lymph node metastasis of LUAD patients. In addition, high expression of TTN-AS1 was correlated with poor postoperative prognosis of LUAD patients. Knockdown of TTN-AS1 significantly inhibited the growth, proliferation, migration, and invasion ability of LUAD cells in vitro. Then, by using bioinformation analysis and luciferase reporter experiment, we identified that TTN-AS1 could function as a competing endogenous RNA (ceRNA) by sponging miR-142-5p to regulate the expression of cyclin-dependent kinase 5 (CDK5) in LUAD. Since CDK5 is a key regulator in the process of epithelial mesenchymal transition (EMT), we detected the expression of EMT-related proteins, consequently, EMT was suppressed by knockdown of TTN-AS1 while this phenomenon was rescued by miR-142-5p inhibitor. Taken above, our study revealed that TTN-AS1 played an important role in LUAD progression. TTN-AS1/miR-142-5p/CDK5 regulatory axis may serve as a novel therapeutic target in the treatment of LUAD.

摘要

越来越多的证据表明，长链非编码 RNA（lncRNA）在人类癌症中调控各种生物学过程中起着关键作用。在许多癌症中，肌联蛋白反义 RNA1（TTN-AS1）被认为是一种促进肿瘤的 lncRNA。然而，TTN-AS1 在肺腺癌（LUAD）中的临床意义和生物学功能尚不清楚。在本研究中，我们揭示了 TTN-AS1 在 LUAD 组织和细胞系中的表达上调。TTN-AS1 高表达与 LUAD 患者的 TNM 分期和淋巴结转移有关。此外，TTN-AS1 高表达与 LUAD 患者术后不良预后相关。TTN-AS1 敲低显著抑制 LUAD 细胞在体外的生长、增殖、迁移和侵袭能力。然后，通过生物信息分析和荧光素酶报告实验，我们发现 TTN-AS1 可以作为竞争性内源性 RNA（ceRNA），通过海绵吸附 miR-142-5p 来调节 LUAD 中细胞周期蛋白依赖性激酶 5（CDK5）的表达。由于 CDK5 是上皮间质转化（EMT）过程中的关键调节因子，我们检测了 EMT 相关蛋白的表达，结果显示，TTN-AS1 敲低抑制 EMT，而 miR-142-5p 抑制剂则可逆转这一现象。综上所述，我们的研究表明 TTN-AS1 在 LUAD 进展中发挥重要作用。TTN-AS1/miR-142-5p/CDK5 调控轴可能成为治疗 LUAD 的新的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ac8/6667499/70974f562ed3/41419_2019_1811_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ac8/6667499/0dc88e9d1833/41419_2019_1811_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ac8/6667499/ab1018f2cccb/41419_2019_1811_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ac8/6667499/609b07cd17b0/41419_2019_1811_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ac8/6667499/d22234958ecf/41419_2019_1811_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ac8/6667499/876494a6cdf0/41419_2019_1811_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ac8/6667499/70974f562ed3/41419_2019_1811_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ac8/6667499/0dc88e9d1833/41419_2019_1811_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ac8/6667499/ab1018f2cccb/41419_2019_1811_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ac8/6667499/609b07cd17b0/41419_2019_1811_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ac8/6667499/d22234958ecf/41419_2019_1811_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ac8/6667499/876494a6cdf0/41419_2019_1811_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ac8/6667499/70974f562ed3/41419_2019_1811_Fig6_HTML.jpg

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[3]
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[6]
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[7]
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本文引用的文献

[1]
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Oncogene. 2019-4-9

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LncRNA-FEZF1-AS1 Promotes Tumor Proliferation and Metastasis in Colorectal Cancer by Regulating PKM2 Signaling.

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