Urinary Exosomal miRNAs as biomarkers of bladder Cancer and experimental verification of mechanism of miR-93-5p in bladder Cancer

Abstract Background Bladder cancer (BC) is one of the most common malignancies globally. Early diagnosis of it can significantly improve patients’ survival and quality of life. Urinary exosomes (UEs)-derived miRNAs might be a promising biomarker for BC detection. Method A total of 12 patients with B...

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Autores principales:	Hao Lin, Xiaojun Shi, Haoran Li, Jialiang Hui, Ruiyu Liu, Zihao Chen, Yuwen Lu, Wanlong Tan
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Bladder cancer Urinary exosomes microRNA Biomarker BTG2 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/660ead234ff14681ba8423381d3674dc
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spelling	oai:doaj.org-article:660ead234ff14681ba8423381d3674dc2021-12-05T12:19:38ZUrinary Exosomal miRNAs as biomarkers of bladder Cancer and experimental verification of mechanism of miR-93-5p in bladder Cancer10.1186/s12885-021-08926-x1471-2407https://doaj.org/article/660ead234ff14681ba8423381d3674dc2021-12-01T00:00:00Zhttps://doi.org/10.1186/s12885-021-08926-xhttps://doaj.org/toc/1471-2407Abstract Background Bladder cancer (BC) is one of the most common malignancies globally. Early diagnosis of it can significantly improve patients’ survival and quality of life. Urinary exosomes (UEs)-derived miRNAs might be a promising biomarker for BC detection. Method A total of 12 patients with BC and 4 non-cancerous participants (as healthy control) were recruited from a single center between March 2018 and December 2019 as the discovery set. Midstream urine samples from each participants were collected and high-throughput sequencing and differentially expression analysis were conducted. Combined with miRNA expression profile of BC tissue from The Cancer Genome Atlas (TCGA), miRNAs biomarkers for BC were determined. Candidate miRNAs as biomarkers were selected followed by verification with a quantitative reverse-transcription polymerase chain reaction assay in an independent validation cohort consisting of 53 BC patients and 51 healthy controls. The receiver-operating characteristic (ROC) curve was established to evaluate the diagnostic performance of UE-derived miRNAs. The possible mechanism of miRNAs were revealed by bioinformatic analysis and explored in vitro experiments. Results We identified that miR-93-5p, miR-516a-5p were simultaneously significantly increased both in UEs from BC compared with healthy control and BC tissue compared with normal tissue, which were verified by RT-qPCR in the validation cohort. Subsequently, the performance to discover BC of the miR-93-5p, miR-516a-5p was further verified with an area under ROC curve (AUC) of 0.838 and 0.790, respectively, which was significantly higher than that of urine cytology (AUC = 0.630). Moreover, miR-93-5p was significantly increased in muscle-invasive BC compared with non-muscle-invasive BC with an AUC of 0.769. Bioinformatic analysis revealed that B-cell translocation gene 2(BTG2) gene may be the hub target gene of miR-93-5p. In vitro experiments verified that miR-93-5p suppressed BTG2 expression and promoted BC cells proliferation, invasion and migration. Conclusion Urine derived exosomes have a distinct miRNA profile in BC patients, and urinary exosomal miRNAs could be used as a promising non-invasive tool to detect BC. In vitro experiments suggested that miR-93-5p overexpression may contribute to BC progression via suppressing BTG2 expression.Hao LinXiaojun ShiHaoran LiJialiang HuiRuiyu LiuZihao ChenYuwen LuWanlong TanBMCarticleBladder cancerUrinary exosomesmicroRNABiomarkerBTG2Neoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENBMC Cancer, Vol 21, Iss 1, Pp 1-17 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Bladder cancer Urinary exosomes microRNA Biomarker BTG2 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Bladder cancer Urinary exosomes microRNA Biomarker BTG2 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Hao Lin Xiaojun Shi Haoran Li Jialiang Hui Ruiyu Liu Zihao Chen Yuwen Lu Wanlong Tan Urinary Exosomal miRNAs as biomarkers of bladder Cancer and experimental verification of mechanism of miR-93-5p in bladder Cancer
description	Abstract Background Bladder cancer (BC) is one of the most common malignancies globally. Early diagnosis of it can significantly improve patients’ survival and quality of life. Urinary exosomes (UEs)-derived miRNAs might be a promising biomarker for BC detection. Method A total of 12 patients with BC and 4 non-cancerous participants (as healthy control) were recruited from a single center between March 2018 and December 2019 as the discovery set. Midstream urine samples from each participants were collected and high-throughput sequencing and differentially expression analysis were conducted. Combined with miRNA expression profile of BC tissue from The Cancer Genome Atlas (TCGA), miRNAs biomarkers for BC were determined. Candidate miRNAs as biomarkers were selected followed by verification with a quantitative reverse-transcription polymerase chain reaction assay in an independent validation cohort consisting of 53 BC patients and 51 healthy controls. The receiver-operating characteristic (ROC) curve was established to evaluate the diagnostic performance of UE-derived miRNAs. The possible mechanism of miRNAs were revealed by bioinformatic analysis and explored in vitro experiments. Results We identified that miR-93-5p, miR-516a-5p were simultaneously significantly increased both in UEs from BC compared with healthy control and BC tissue compared with normal tissue, which were verified by RT-qPCR in the validation cohort. Subsequently, the performance to discover BC of the miR-93-5p, miR-516a-5p was further verified with an area under ROC curve (AUC) of 0.838 and 0.790, respectively, which was significantly higher than that of urine cytology (AUC = 0.630). Moreover, miR-93-5p was significantly increased in muscle-invasive BC compared with non-muscle-invasive BC with an AUC of 0.769. Bioinformatic analysis revealed that B-cell translocation gene 2(BTG2) gene may be the hub target gene of miR-93-5p. In vitro experiments verified that miR-93-5p suppressed BTG2 expression and promoted BC cells proliferation, invasion and migration. Conclusion Urine derived exosomes have a distinct miRNA profile in BC patients, and urinary exosomal miRNAs could be used as a promising non-invasive tool to detect BC. In vitro experiments suggested that miR-93-5p overexpression may contribute to BC progression via suppressing BTG2 expression.
format	article
author	Hao Lin Xiaojun Shi Haoran Li Jialiang Hui Ruiyu Liu Zihao Chen Yuwen Lu Wanlong Tan
author_facet	Hao Lin Xiaojun Shi Haoran Li Jialiang Hui Ruiyu Liu Zihao Chen Yuwen Lu Wanlong Tan
author_sort	Hao Lin
title	Urinary Exosomal miRNAs as biomarkers of bladder Cancer and experimental verification of mechanism of miR-93-5p in bladder Cancer
title_short	Urinary Exosomal miRNAs as biomarkers of bladder Cancer and experimental verification of mechanism of miR-93-5p in bladder Cancer
title_full	Urinary Exosomal miRNAs as biomarkers of bladder Cancer and experimental verification of mechanism of miR-93-5p in bladder Cancer
title_fullStr	Urinary Exosomal miRNAs as biomarkers of bladder Cancer and experimental verification of mechanism of miR-93-5p in bladder Cancer
title_full_unstemmed	Urinary Exosomal miRNAs as biomarkers of bladder Cancer and experimental verification of mechanism of miR-93-5p in bladder Cancer
title_sort	urinary exosomal mirnas as biomarkers of bladder cancer and experimental verification of mechanism of mir-93-5p in bladder cancer
publisher	BMC
publishDate	2021
url	https://doaj.org/article/660ead234ff14681ba8423381d3674dc
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Urinary Exosomal miRNAs as biomarkers of bladder Cancer and experimental verification of mechanism of miR-93-5p in bladder Cancer

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