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A novel risk score model based on five angiogenesis-related long non-coding RNAs for bladder urothelial carcinoma

BACKGROUND: Tumour angiogenesis is an independent risk factor for bladder urothelial carcinoma (BUC) progression, but viable and promising antiangiogenic targets are understudied. Emerging evidence suggests that long non-coding RNAs (lncRNAs) play prominent role in the tumour microenvironment and tu...

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Autores principales: Li, Xinyuan, Zhang, Chunlin, Peng, Xiang, Li, Yang, Chen, Guo, Gou, Xin, Zhou, Xiang, Ma, Chao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9019982/
https://www.ncbi.nlm.nih.gov/pubmed/35440045
http://dx.doi.org/10.1186/s12935-022-02575-1
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author Li, Xinyuan
Zhang, Chunlin
Peng, Xiang
Li, Yang
Chen, Guo
Gou, Xin
Zhou, Xiang
Ma, Chao
author_facet Li, Xinyuan
Zhang, Chunlin
Peng, Xiang
Li, Yang
Chen, Guo
Gou, Xin
Zhou, Xiang
Ma, Chao
author_sort Li, Xinyuan
collection PubMed
description BACKGROUND: Tumour angiogenesis is an independent risk factor for bladder urothelial carcinoma (BUC) progression, but viable and promising antiangiogenic targets are understudied. Emerging evidence suggests that long non-coding RNAs (lncRNAs) play prominent role in the tumour microenvironment and tumour angiogenesis. METHODS: The clinical data of BUC patients were obtained from TCGA database and clinical specimens of 138 BUC patients. Univariate and multivariate COX regression analyses were used to identify survival-related ARLNRs (sARLNRs) from The Molecular Signatures Database v4.0. Fisher’s exact probability method was used to detect the correlations between sARLNRs levels and clinicopathological characteristics. A chain of experiments including FACS, qPCR, immunohistochemistry, tube formation, migration and invasion assays, combining with co-culture models, were utilized to validate the clinical significance and angiogenetic correlation of sARLNRs. RESULTS: Five sARLNRs were employed to establish an angiogenesis-related risk score model, by which patients in the low-risk group obtained better overall survival than those in the high-risk group. The expression of AC005625.1 and AC008760.1 was significantly related to ECs percentage, tumour size and muscle invasion status. Besides, AC005625.1 and AC008760.1 expressed lower in BUC cell lines and tumour tissues than that in normal urothelial cells and adjacent normal tissues, with much lower levels in more advanced T stages. A prominently higher proportion of ECs was detected in tumour tissues with lower expression of AC005625.1 and AC008760.1. In the co-culture models, we found that knockdown of AC005625.1 and AC008760.1 in BUC cells increased the tube formation, migration and invasion abilities of HUVEC. The expression levels of CD31, VEGF-A, VIMENTIN and N-CADHERIN were also enhanced in HUVEC cells co-cultured with siR-AC005625.1 and siR-AC008760.1-treated T24 cells. CONCLUSION: In the study, we identify five sARLNRs and validate their clinical significance, angiogenesis correlation and prognosis-predictive values in BUC. These findings may provide a new perspective and some promising antiangiogenic targets for clinical diagnosis and treatment strategies of BUC. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12935-022-02575-1.
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spelling pubmed-90199822022-04-21 A novel risk score model based on five angiogenesis-related long non-coding RNAs for bladder urothelial carcinoma Li, Xinyuan Zhang, Chunlin Peng, Xiang Li, Yang Chen, Guo Gou, Xin Zhou, Xiang Ma, Chao Cancer Cell Int Primary Research BACKGROUND: Tumour angiogenesis is an independent risk factor for bladder urothelial carcinoma (BUC) progression, but viable and promising antiangiogenic targets are understudied. Emerging evidence suggests that long non-coding RNAs (lncRNAs) play prominent role in the tumour microenvironment and tumour angiogenesis. METHODS: The clinical data of BUC patients were obtained from TCGA database and clinical specimens of 138 BUC patients. Univariate and multivariate COX regression analyses were used to identify survival-related ARLNRs (sARLNRs) from The Molecular Signatures Database v4.0. Fisher’s exact probability method was used to detect the correlations between sARLNRs levels and clinicopathological characteristics. A chain of experiments including FACS, qPCR, immunohistochemistry, tube formation, migration and invasion assays, combining with co-culture models, were utilized to validate the clinical significance and angiogenetic correlation of sARLNRs. RESULTS: Five sARLNRs were employed to establish an angiogenesis-related risk score model, by which patients in the low-risk group obtained better overall survival than those in the high-risk group. The expression of AC005625.1 and AC008760.1 was significantly related to ECs percentage, tumour size and muscle invasion status. Besides, AC005625.1 and AC008760.1 expressed lower in BUC cell lines and tumour tissues than that in normal urothelial cells and adjacent normal tissues, with much lower levels in more advanced T stages. A prominently higher proportion of ECs was detected in tumour tissues with lower expression of AC005625.1 and AC008760.1. In the co-culture models, we found that knockdown of AC005625.1 and AC008760.1 in BUC cells increased the tube formation, migration and invasion abilities of HUVEC. The expression levels of CD31, VEGF-A, VIMENTIN and N-CADHERIN were also enhanced in HUVEC cells co-cultured with siR-AC005625.1 and siR-AC008760.1-treated T24 cells. CONCLUSION: In the study, we identify five sARLNRs and validate their clinical significance, angiogenesis correlation and prognosis-predictive values in BUC. These findings may provide a new perspective and some promising antiangiogenic targets for clinical diagnosis and treatment strategies of BUC. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12935-022-02575-1. BioMed Central 2022-04-19 /pmc/articles/PMC9019982/ /pubmed/35440045 http://dx.doi.org/10.1186/s12935-022-02575-1 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Primary Research
Li, Xinyuan
Zhang, Chunlin
Peng, Xiang
Li, Yang
Chen, Guo
Gou, Xin
Zhou, Xiang
Ma, Chao
A novel risk score model based on five angiogenesis-related long non-coding RNAs for bladder urothelial carcinoma
title A novel risk score model based on five angiogenesis-related long non-coding RNAs for bladder urothelial carcinoma
title_full A novel risk score model based on five angiogenesis-related long non-coding RNAs for bladder urothelial carcinoma
title_fullStr A novel risk score model based on five angiogenesis-related long non-coding RNAs for bladder urothelial carcinoma
title_full_unstemmed A novel risk score model based on five angiogenesis-related long non-coding RNAs for bladder urothelial carcinoma
title_short A novel risk score model based on five angiogenesis-related long non-coding RNAs for bladder urothelial carcinoma
title_sort novel risk score model based on five angiogenesis-related long non-coding rnas for bladder urothelial carcinoma
topic Primary Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9019982/
https://www.ncbi.nlm.nih.gov/pubmed/35440045
http://dx.doi.org/10.1186/s12935-022-02575-1
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