Qin Jia-Xin, Liu Xing, Wang Xin-Lei, Wang Guang-Yue, Liang Qing, Dong Yang, Pang Kun, Hao Lin, Xue Liang, Zhao Yan, Hu Zheng-Xiang, Li Rui, Lv Qian, Chao Liu, Meng Fan-Lai, Shi Zhen-Duo, Han Cong-Hui
Department of Urology, Xuzhou Clinical College of Xuzhou Medical University, Xuzhou, China.
Department of Urology, Xuzhou Central Hospital, Xuzhou, China.
Front Genet. 2022 Sep 19;13:984279. doi: 10.3389/fgene.2022.984279. eCollection 2022.
With the continued advancement of RNA-seq (RNA-sequencing), microRNA (miRNA) editing events have been demonstrated to play an important role in different malignancies. However, there is yet no description of the miRNA editing events in recurrent bladder cancer. To identify and compare miRNA editing events in primary and recurrent bladder cancer, as well as to investigate the potential molecular mechanism and its impact on patient prognosis. We examined the mRNA and miRNA transcriptomes of 12 recurrent bladder cancer cases and 13 primary bladder cancer cases. The differentially expressed mRNA sequences were analyzed. Furthermore, we identified the differentially expressed genes (DEGs) in recurrent bladder cancer. The Gene Ontology (GO) functional enrichment analyses on DEGs and gene set enrichment analysis were performed. The consensus molecular subtype (CMS) classification of bladder cancer was identified using the Consensus MIBC package in R (4.1.0); miRNA sequences were then further subjected to differentially expressed analysis and pathway enrichment analysis. MiRNA editing events were identified using miRge3.0. miRDB and TargetScanHuman were used to predict the downstream targets of specific differentially edited or expressed miRNAs. The expression levels of miR-154-5p and ADAR were validated by RT-qPCR. Finally, survival and co-expression studies were performed on the TCGA-BLCA cohort. First, the mRNA expression levels in recurrent bladder cancer changed significantly, supporting progression via related molecular signal pathways. Second, significantly altered miRNAs in recurrent bladder cancer were identified, with miR-154-5p showing the highest level of editing in recurrent bladder cancer and may up-regulate the expression levels of downstream targets HS3ST3A1, AQP9, MYLK, and RAB23. The survival analysis results of TCGA data revealed that highly expressed HS3ST3A1 and RAB23 exhibited poor prognosis. In addition, miR-154 editing events were found to be significant to CMS classification. MiRNA editing in recurrent bladder cancer was detected and linked with poor patient prognosis, providing a reference for further uncovering the intricate molecular mechanism in recurrent bladder cancer. Therefore, inhibiting A-to-I editing of miRNA may be a viable target for bladder cancer treatment, allowing current treatment choices to be expanded and individualized.
随着RNA测序（RNA-seq）技术的不断进步，微小RNA（miRNA）编辑事件已被证明在不同恶性肿瘤中发挥重要作用。然而，目前尚无关于复发性膀胱癌中miRNA编辑事件的描述。为了识别和比较原发性和复发性膀胱癌中的miRNA编辑事件，并研究其潜在的分子机制及其对患者预后的影响。我们检测了12例复发性膀胱癌病例和13例原发性膀胱癌病例的mRNA和miRNA转录组。对差异表达的mRNA序列进行了分析。此外，我们鉴定了复发性膀胱癌中差异表达的基因（DEG）。对DEG进行了基因本体（GO）功能富集分析和基因集富集分析。使用R（4.1.0）中的Consensus MIBC软件包对膀胱癌进行共识分子亚型（CMS）分类；然后对miRNA序列进一步进行差异表达分析和通路富集分析。使用miRge3.0鉴定miRNA编辑事件。使用miRDB和TargetScanHuman预测特定差异编辑或表达的miRNA的下游靶标。通过RT-qPCR验证miR-154-5p和ADAR的表达水平。最后，对TCGA-BLCA队列进行了生存和共表达研究。首先，复发性膀胱癌中的mRNA表达水平发生了显著变化，支持通过相关分子信号通路进展。其次，鉴定出复发性膀胱癌中显著改变的miRNA，其中miR-154-5p在复发性膀胱癌中显示出最高水平的编辑，并且可能上调下游靶标HS3ST3A1、AQP9、MYLK和RAB23的表达水平。TCGA数据的生存分析结果显示，高表达的HS3ST3A1和RAB23预后较差。此外，发现miR-154编辑事件对CMS分类具有重要意义。检测到复发性膀胱癌中的miRNA编辑，并与患者预后不良相关，为进一步揭示复发性膀胱癌复杂的分子机制提供了参考。因此，抑制miRNA的A到I编辑可能是膀胱癌治疗的一个可行靶点，从而扩大当前的治疗选择并实现个体化。
