Prognostic and clinicopathological significance of long noncoding RNA CTD-2510F5.4 in gastric cancer

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Abstract

Background

Compelling studies have demonstrated the correlation between aberrant expressed lncRNAs and human cancers, and revealed promise of these lncRNAs as biomarkers in predicting patients’ survival and outcome.

Methods

We downloaded the RNA-seq data from the Cancer Genome Atlas, and screened out DEGs and DELs between gastric cancer tissues and normal gastric tissues. By bioinformatics analysis, we identified CTD-2510F5.4 was a malignant phenotype associated lncRNA. The expression levels of CTD-2510F5.4 in tissues were detected by ISH, and the relationships between CTD-2510F5.4 expression and clinicopathological characteristics were analyzed by statistical analysis.

Results

By bioinformatics analysis and functional analysis, we identified CTD-2510F5.4 was a malignant phenotype associated lncRNA of gastric cancer that potentially regulated cell cycle and apoptosis. CTD-2510F5.4 expression was significantly higher in gastric cancers, and was correlated with pathological grade, vascular or nerve invasion, AJCC TNM stage and OS. Moreover, gastric cancer patients with high CTD-2510F5.4 expression showed significantly shorter MST. High CTD-2510F5.4 expression was a independent risk factor for gastric cancers at pathological grade < III and without vascular or nerve invasion.

Conclusions

We identified CTD-2510F5.4 was a malignant phenotype associated lncRNA potentially involved in the pathogenesis of gastric cancer. Our data also supported the clinical potential of CTD-2510F5.4 being a diagnostic and prognostic biomarker for gastric cancer.

Electronic supplementary material

The online version of this article (10.1007/s10120-018-00911-x) contains supplementary material, which is available to authorized users.

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Most cited references 24

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Up-regulated long non-coding RNA H19 contributes to proliferation of gastric cancer cells.

Feng Yang, Jianwei Bi, Xuchao Xue … (2012)

Long non-coding RNAs (lncRNAs) have been shown to have important regulatory roles in cancer biology, and the lncRNA H19 is up-regulated in hypoxic stress and in some tumors. However, the contributions of H19 to gastric cancer remain largely unknown. In this study, we assayed the H19 expression level in gastric cancer tissues by real-time PCR, and defined the biological functions by flow cytometry and RNA immunoprecipitation. We demonstrated that H19 levels were markedly increased in gastric cancer cells and gastric cancer tissues compared with normal controls. Moreover, ectopic expression of H19 increased cell proliferation, whereas H19 siRNA treatment contributed to cell apoptosis in AGS cell line. We further verified that H19 was associated with p53, and that this association resulted in partial p53 inactivation. These data suggest an important role for H19 in the molecular etiology of gastric cancer and potential application of H19 in gastric cancer therapy. © 2012 The Authors Journal compilation © 2012 FEBS.

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Long noncoding RNA ANRIL indicates a poor prognosis of gastric cancer and promotes tumor growth by epigenetically silencing of miR-99a/miR-449a

Er-bao Zhang, Rong Kong, Dan-dan Yin … (2014)

Long noncoding RNAs are involved in diseases including cancer. Here, we reported that ANRIL (CDKN2B-AS1), a 3.8-kb long noncoding RNA, recruiting and binding to PRC2, was generally upregulated in human gastric cancer (GC) tissues. In a cohort of 120 GC patients, the higher expression of ANRIL was significantly correlated with a higher TNM stage (P=0.041) and tumor size (P=0.001). Multivariate analyses revealed that ANRIL expression served as an independent predictor for overall survival (P=0.036). Further experiments revealed that ANRIL knockdown significantly repressed the proliferation both in vitro and in vivo. We also showed that E2F1 could induce ANRIL and ANRIL-mediated growth promotion is in part due to epigenetic repression of miR-99a/miR-449a in Trans (controlling the targets—mTOR and CDK6/E2F1 pathway) by binding to PRC2, thus forming a positive feedback loop, continuing to promote GC cell proliferation. To our knowledge, this is the first report showed that the role of ANRIL in the progression of GC and ANRIL could crosstalk with microRNAs in epigenetic level. Our results suggest that ANRIL, as a growth regulator, may serve as a candidate prognostic biomarker and target for new therapies in human gastric cancer.

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A Positive Feedback Loop of lncRNA-PVT1 and FOXM1 Facilitates Gastric Cancer Growth and Invasion.

Zhaohui Huang, Yiqin Wang, Weiwei Weng … (2017)

Purpose: The long, noncoding RNA (lncRNA) PVT1 is an important epigenetic regulator with a critical role in human tumors. Here, we aimed to investigate the clinical application and the potential molecular mechanisms of PVT1 in gastric cancer tumorigenesis and progression.Experimental Design: The expression level of PVT1 was determined by RT-qPCR analysis in 190 pairs of gastric cancer tissues and adjacent normal gastric mucosa tissues (ANT). The biologic functions of PVT1 were assessed by in vitro and in vivo functional experiments. RNA protein pull-down assays and LS/MS mass spectrometry analysis were performed to detect and identify the PVT1- interacting protein FOXM1. Protein-RNA immunoprecipitation assays were conducted to examine the interaction of FOXM1 and PVT1 Chromatin immunoprecipitation (ChIP) and luciferase analyses were utilized to identify the binding site of FOXM1 on the PVT1 promoter.Results: The lncRNA PVT1 was significantly upregulated in gastric cancer tissues compared with ANTs. High expression of PVT1 predicted poor prognosis in patients with gastric cancer. PVT1 enhanced gastric cancer cell proliferation and invasion in vitro and in vivoPVT1 directly bound FOXM1 protein and increased FOXM1 posttranslationally. Moreover, PVT1 is also a FOXM1-responsive lncRNA, and FOXM1 directly binds to the PVT1 promoter to activate its transcription. Finally, PVT1 fulfilled its oncogenic functions in a FOXM1-mediated manner.Conclusions: Our study suggests that PVT1 promotes tumor progression by interacting with FOXM1. PVT1 may be a valuable prognostic predictor for gastric cancer, and the positive feedback loop of PVT1-FOXM1 could be a therapeutic target in pharmacologic strategies. Clin Cancer Res; 23(8); 2071-80. ©2016 AACR.

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Author and article information

Contributors

Baoli Qin:

ORCID: http://orcid.org/0000-0003-2591-1217

+86-18900917822 , poryqin@126.com

Journal

Journal ID (nlm-ta): Gastric Cancer

Journal ID (iso-abbrev): Gastric Cancer

Title: Gastric Cancer

Publisher: Springer Singapore (Singapore )

ISSN (Print): 1436-3291

ISSN (Electronic): 1436-3305

Publication date (Electronic): 17 December 2018

Publication date PMC-release: 17 December 2018

Publication date (Print): 2019

Volume: 22

Issue: 4

Pages: 692-704

Affiliations

ISNI 0000 0004 1798 5889, GRID grid.459742.9, Medical Oncology Department of Gastrointestinal Cancer (1), , Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, ; NO.44 Xiaoheyan Road, Dadong District, Shenyang, 110042 Liaoning People’s Republic of China

Author information

Baoli Qin http://orcid.org/0000-0003-2591-1217

Article

Publisher ID: 911

DOI: 10.1007/s10120-018-00911-x

PMC ID: 6570689

PubMed ID: 30560474

SO-VID: cae8a859-b742-4feb-8011-412123d83e44

License:

OpenAccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

History

Date received : 24 April 2018

Date accepted : 2 December 2018

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issue-copyright-statement © The International Gastric Cancer Association and The Japanese Gastric Cancer Association 2019

ScienceOpen disciplines: Oncology & Radiotherapy

Keywords: lncrnas,bioinformatics analysis,ctd-2510f5.4,biomarker,gastric cancer

Data availability:

ScienceOpen disciplines: Oncology & Radiotherapy

Keywords: lncrnas, bioinformatics analysis, ctd-2510f5.4, biomarker, gastric cancer

Prognostic and clinicopathological significance of long noncoding RNA CTD-2510F5.4 in gastric cancer

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Abstract

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Karger: Oncology

Most cited references 24

Up-regulated long non-coding RNA H19 contributes to proliferation of gastric cancer cells.

Long noncoding RNA ANRIL indicates a poor prognosis of gastric cancer and promotes tumor growth by epigenetically silencing of miR-99a/miR-449a

A Positive Feedback Loop of lncRNA-PVT1 and FOXM1 Facilitates Gastric Cancer Growth and Invasion.

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