Author:
Zhong Chen,Yu Qian,Peng Yucong,Zhou Shengjun,Liu Zhendong,Deng Yong,Guo Leiguang,Zhao Shiguang,Chen Gao
Abstract
Abstract
Background
Long noncoding RNAs (lncRNAs) contribute to multiple biological processes in human glioblastoma (GBM). However, identifying a specific lncRNA target remains a challenge. In this study, bioinformatics methods and competing endogenous RNA (ceRNA) network regulatory rules were used to identify GBM-related lncRNAs and revealed that OXCT1 antisense RNA 1 (OXCT1-AS1) is a potential therapeutic target for the treatment of glioma.
Methods
Based on the Gene Expression Omnibus (GEO) dataset, we identified differential lncRNAs, microRNAs and mRNAs and constructed an lncRNA-associated ceRNA network.
The novel lncRNA OXCT1-AS1 was proposed to function as a ceRNA, and its potential target miRNAs were predicted through the database LncBase Predicted v.2. The expression patterns of OXCT1-AS1 in glioma and normal tissue samples were measured. The effect of OXCT1-AS1 on glioma cells was checked using the Cell Counting Kit 8 assay, cell colony formation assay, Transwell assay and flow cytometry in vitro. The dual-luciferase activity assay was performed to investigate the potential mechanism of the ceRNA network. Finally, orthotopic mouse models of glioma were created to evaluate the influence of OXCT1-AS1 on tumour growth in vivo.
Results
In this study, it was found that the expression of lncRNA OXCT1-AS1 was upregulated in both The Cancer Genome Atlas (TCGA) GBM patients and GBM tissue samples, and high expression of OXCT1-AS1 predicted a poor prognosis. Suppressing OXCT1-AS1 expression significantly decreased GBM cell proliferation and inhibited cell migration and invasion. We further investigated the potential mechanism and found that OXCT1-AS1 may act as a ceRNA of miR-195 to enhance CDC25A expression and promote glioma cell progression. Finally, knocking down OXCT1-AS1 notably attenuated the severity of glioma in vivo.
Conclusion
OXCT1-AS1 inhibits glioma progression by regulating the miR-195-5p/CDC25A axis and is a specific tumour marker and a novel potential therapeutic target for glioma treatment.
Funder
China Postdoctoral Science Foundation
National Key R&D program of China
Key Research and Development Project of Zhejiang Province
TCM Key Discipline of Zhejiang province
Publisher
Springer Science and Business Media LLC
Reference42 articles.
1. Mary D. Glioblastoma: overview of disease and treatment. Clin J Oncol Nurs. 2016;20(5 Suppl):S2–8.
2. Brandner S, Jaunmuktane Z. Neurological update: gliomas and other primary brain tumours in adults. J Neurol. 2018;265(3):717–27. https://doi.org/10.1007/s00415-017-8652-3.
3. Chen R, Smith-Cohn M, Cohen AL, Colman H. Glioma subclassifications and their clinical significance. Neurotherapeutics. 2017;14(2):1–14.
4. Alan O, Telli TA, Tuylu TB, Arikan R, Demircan NC, Ercelep O, et al. Prognostic factors in progressive high-grade glial tumors treated with systemic approach: A single center experience. J Oncol Pharm Pract. 2020;0(0):1078155220920684.
5. Jiang HH, Lin S. Current status and prospect in the treatment of glioblastoma. Zhonghua wai ke za zhi Chinese J Surg. 2020;58(1):70–4. https://doi.org/10.3760/cma.j.issn.0529-5815.2020.01.015.
Cited by
29 articles.
订阅此论文施引文献
订阅此论文施引文献，注册后可以免费订阅5篇论文的施引文献，订阅后可以查看论文全部施引文献