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STAT1 诱导的长链非编码 RNA KTN1-AS1 上调预测非小细胞肺癌不良预后并通过 miR-23b/DEPDC1 轴促进其进展。

STAT1-induced upregulation of lncRNA KTN1-AS1 predicts poor prognosis and facilitates non-small cell lung cancer progression via miR-23b/DEPDC1 axis.

机构信息

Department of Oncology, Binzhou Medical University Hospital, Binzhou, Shandong, China.

Department of Hepatobiliary Surgery, Shandong Provincial ENT Hospital, Shandong Provincial ENT Hospital Affiliated to Shandong University, Jinan, Shandong, China.

出版信息

Aging (Albany NY). 2020 May 12;12(9):8680-8701. doi: 10.18632/aging.103191.

DOI:10.18632/aging.103191
PMID:32396871
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7244022/
Abstract

Several of the thousands of long noncoding RNAs (lncRNAs) have been functionally characterized in various tumors. In this study, we aimed to explore the function and possible molecular mechanism of lncRNA KTN1 antisense RNA 1 (KTN1-AS1) involved in non-small cell lung cancer (NSCLC). We identified a novel NSCLC-related lncRNA, KTN1 antisense RNA 1 (KTN1-AS1) which was demonstrated to be distinctly highly expressed in NSCLC. KTN1-AS1 upregulation was induced by STAT1. Clinical study also suggested that higher levels of KTN1-AS1 were associated with advanced clinical progression and a shorter five-year overall survival. Functionally, loss-of-function assays with in vitro and in vivo experiments revealed that KTN1-AS1 promoted the proliferation, migration, invasion and EMT progress of NSCLC cells, and suppressed apoptosis. Mechanistic studies indicated that miR-23b was a direct target of KTN1-AS1, which functioned as a ceRNA to subsequently facilitate miR-23b's target gene DEPDC1 expression in NSCLC cells. Rescue experiments confirmed that KTN1-AS1 overexpression could increase the colony formation and migration ability suppressed by miR-23b upregulation in NSCLC cells. Overall, our findings imply that STAT1-induced upregulation of KTN1-AS1 display tumor-promotive roles in NSCLC progression via regulating miR-23b/DEPDC1 axis, suggesting that KTN1-AS1 may be a novel biomarker and therapeutic target for NSCLC patients.

摘要

数千个长链非编码 RNA（lncRNA）中的几个已在各种肿瘤中具有功能特征。在这项研究中，我们旨在探索 lncRNA KTN1 反义 RNA 1（KTN1-AS1）在非小细胞肺癌（NSCLC）中涉及的功能和可能的分子机制。我们鉴定了一种新型 NSCLC 相关 lncRNA，KTN1 反义 RNA 1（KTN1-AS1），其在 NSCLC 中表现出明显高表达。STAT1 诱导 KTN1-AS1 的上调。临床研究还表明，较高水平的 KTN1-AS1 与晚期临床进展和较短的五年总生存率相关。功能丧失实验以及体外和体内实验表明，KTN1-AS1 促进 NSCLC 细胞的增殖、迁移、侵袭和 EMT 进展，并抑制细胞凋亡。机制研究表明，miR-23b 是 KTN1-AS1 的直接靶标，它作为 ceRNA 随后促进 NSCLC 细胞中 miR-23b 的靶基因 DEPDC1 的表达。挽救实验证实，KTN1-AS1 的过表达可以增加 NSCLC 细胞中 miR-23b 上调抑制的集落形成和迁移能力。总的来说，我们的研究结果表明，STAT1 诱导的 KTN1-AS1 上调通过调节 miR-23b/DEPDC1 轴在 NSCLC 进展中发挥肿瘤促进作用，表明 KTN1-AS1 可能是 NSCLC 患者的新型生物标志物和治疗靶标。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9181/7244022/0dc35a7dec6a/aging-12-103191-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9181/7244022/a3f43485698f/aging-12-103191-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9181/7244022/60051d7a7559/aging-12-103191-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9181/7244022/a7d91f9b823f/aging-12-103191-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9181/7244022/04fede48b514/aging-12-103191-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9181/7244022/314976633293/aging-12-103191-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9181/7244022/2ecd3053d549/aging-12-103191-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9181/7244022/2976fa5a1637/aging-12-103191-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9181/7244022/0dc35a7dec6a/aging-12-103191-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9181/7244022/a3f43485698f/aging-12-103191-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9181/7244022/60051d7a7559/aging-12-103191-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9181/7244022/a7d91f9b823f/aging-12-103191-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9181/7244022/04fede48b514/aging-12-103191-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9181/7244022/314976633293/aging-12-103191-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9181/7244022/2ecd3053d549/aging-12-103191-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9181/7244022/2976fa5a1637/aging-12-103191-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9181/7244022/0dc35a7dec6a/aging-12-103191-g008.jpg

相似文献

[1]
STAT1-induced upregulation of lncRNA KTN1-AS1 predicts poor prognosis and facilitates non-small cell lung cancer progression via miR-23b/DEPDC1 axis.

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[6]
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[7]
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引用本文的文献

[1]
The regulatory role and therapeutic potential of long non-coding RNA in non-small cell lung cancer.

J Cancer. 2025-1-6

[2]
Non-Coding RNA as a Biomarker in Lung Cancer.

Noncoding RNA. 2024-9-30

[3]
Roles of DEPDC1 in various types of cancer (Review).

Oncol Lett. 2024-8-29

[4]
Comprehensive analysis and validation reveal DEPDC1 as a potential diagnostic biomarker associated with tumor immunity in non-small-cell lung cancer.

PLoS One. 2024

[5]
Targeting DEP domain containing 1 in anaplastic thyroid carcinoma: Implications for stemness regulation and malignant phenotype suppression.

Heliyon. 2024-2-29

[6]
LncRNAs in non-small cell lung cancer: novel diagnostic and prognostic biomarkers.

Front Mol Biosci. 2023-12-13

[7]
LncRNA KTN1-AS1 facilitates esophageal squamous cell carcinoma progression via miR-885-5p/STRN3 axis.

Genes Genomics. 2024-2

[8]
Long non‑coding RNAs as potential therapeutic targets in non‑small cell lung cancer (Review).

Int J Mol Med. 2023-8

[9]
A novel immunogenomic classification for prognosis in non-small cell lung cancer.

J Cancer Res Clin Oncol. 2023-9

[10]
Long Non-coding RNA KTN1-AS1 Targets miR-505 to Promote Glioblastoma Progression.

Behav Neurol. 2023-1-31

本文引用的文献

[1]
Long noncoding RNA LINC00657 induced by SP1 contributes to the non-small cell lung cancer progression through targeting miR-26b-5p/COMMD8 axis.

J Cell Physiol. 2020-4

[2]
lncRNA DLEU2 modulates cell proliferation and invasion of non-small cell lung cancer by regulating miR-30c-5p/SOX9 axis.

Aging (Albany NY). 2019-9-20

[3]
DEPDC1 promotes cell proliferation and suppresses sensitivity to chemotherapy in human hepatocellular carcinoma.

Biosci Rep. 2019-7-10

[4]
STAT1-induced upregulation of LINC00467 promotes the proliferation migration of lung adenocarcinoma cells by epigenetically silencing DKK1 to activate Wnt/β-catenin signaling pathway.

Biochem Biophys Res Commun. 2019-4-23

[5]
LncRNA KTN1-AS1 promotes tumor growth of hepatocellular carcinoma by targeting miR-23c/ERBB2IP axis.

Biomed Pharmacother. 2018-11-6

[6]
Systematic identification of non-coding pharmacogenomic landscape in cancer.

Nat Commun. 2018-8-9

[7]
Lentinan as an immunotherapeutic for treating lung cancer: a review of 12 years clinical studies in China.

J Cancer Res Clin Oncol. 2018-7-24

[8]
MiR-23b-3p induces the proliferation and metastasis of esophageal squamous cell carcinomas cells through the inhibition of EBF3.

Acta Biochim Biophys Sin (Shanghai). 2018-6-1

[9]
STAT1-mediated upregulation of lncRNA LINC00174 functions a ceRNA for miR-1910-3p to facilitate colorectal carcinoma progression through regulation of TAZ.

Gene. 2018-5-3

[10]
Cytoplasmic functions of long noncoding RNAs.

Wiley Interdiscip Rev RNA. 2018-3-8

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