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

作者全名："Li, Xinyuan; Zhang, Chunlin; Peng, Xiang; Li, Yang; Chen, Guo; Gou, Xin; Zhou, Xiang; Ma, Chao"

作者地址："[Li, Xinyuan; Zhang, Chunlin; Peng, Xiang; Li, Yang; Chen, Guo; Gou, Xin; Zhou, Xiang; Ma, Chao] Chongqing Med Univ, Affiliated Hosp 1, Dept Urol, 1 Youyi Rd, Chongqing 400016, Peoples R China; [Li, Xinyuan] Chinese Acad Sci, Shanghai Inst Biochem & Cell Biol, CAS Ctr Excellence Mol Cell Sci, Shanghai, Peoples R China; [Ma, Chao] Fifth Peoples Hosp Chongqing, Chongqing, Peoples R China; [Zhang, Chunlin; Peng, Xiang; Li, Yang; Chen, Guo; Zhou, Xiang] Chongqing Key Lab Mol Oncol & Epigenet, Chongqing, Peoples R China"

通信作者："Zhou, X; Ma, C (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, Dept Urol, 1 Youyi Rd, Chongqing 400016, Peoples R China.; Ma, C (通讯作者)，Fifth Peoples Hosp Chongqing, Chongqing, Peoples R China.; Zhou, X (通讯作者)，Chongqing Key Lab Mol Oncol & Epigenet, Chongqing, Peoples R China."

来源：CANCER CELL INTERNATIONAL

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:000784986300004

JCR分区：Q1

影响因子：5.8

年份：2022

卷号：22

期号：1

开始页：　

结束页：　

文献类型：Article

关键词：Bladder urothelial carcinoma; Angiogenesis; Tumour microenvironment; Long noncoding RNA; Risk model; Prognosis

摘要："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."

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