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

作者：Hao Lin, Xiaojun Shi, Haoran Li, Jialiang Hui, Ruiyu Liu, Zihao Chen, Yuwen Lu, Wanlong Tan · 发表于：BMC Cancer · 年份：2021 · DOI：10.1186/s12885-021-08926-x · 被引用次数：60 · 研究领域：Extracellular vesicles in disease、Cancer-related molecular mechanisms research、Bladder and Urothelial Cancer Treatments

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, ...