拥有46个微小RNA（miRNA）串联嵌入的长度约为100 kb，19号染色体微小RNA簇（C19MC）是人类基因组中最大的miRNA簇。C19MC从一个长链非编码基因组区域转录，并通常同时高水平表达。因此，我们进行了综合多组学数据分析，以研究C19MC的调控、表达模式及其对膀胱癌（BCa）的影响。我们发现，C19MC的43个成员在BCa中高度表达。然而，它与经常复发的拷贝数变异（CNV）增益的共定位在统计上不显著，无法证明其上调。有报道称，C19MC的表达受到一个位于转录起始位点的17.6 kb上游的已建立的CpG岛的调控，但我们发现该岛上的CpG探针为低甲基化，在BCa队列中没有统计学上的显著性。此外，C19MC的启动子区域受到七种转录因子（NR2F6、SREBF1、TBP、GATA3、GABPB1、ETV4和ZNF444）和五种染色质修饰因子（SMC3、KDMA1、EZH2、RAD21和CHD7）的强调控。有趣的是，我们发现这12个基因在BCa患者中过表达。此外，C19MC与42个TSG（tumor suppressor gene，抑癌基因）靶点对应且被下调，其中15个与患者生存显著相关。我们的发现表明，启动子区域的转录因子和染色质修饰因子可能调控C19MC的过表达。过表达的C19MC成员、转录调控因子和TSG基因可进一步作为潜在的诊断和预后指标，以及BCa的治疗管理策略。©2023年。作者。

With 46 microRNAs (miRNAs) embedded tandemly over a distance of ~100 kb, chromosome 19 microRNA cluster (C19MC) is the largest miRNA cluster in the human genome. The C19MC is transcribed from a long noncoding genomic region and is usually expressed simultaneously at a higher level. Hence, we performed an integrative multiomics data analysis to examine C19MC regulation, expression patterns, and their impact on bladder cancer (BCa). We found that 43 members of C19MC were highly expressed in BCa. However, its co-localization with recurrent copy number variation (CNV) gain was not statistically significant to implicate its upregulation. It has been reported that C19MC expression is regulated by a well-established CpG island situated 17.6 kb upstream of the transcription start site, but we found that CpG probes at this island were hypomethylated, which was not statistically significant in the BCa cohort. In addition, the promoter region of C19MC is strongly regulated by a group of seven transcription factors (NR2F6, SREBF1, TBP, GATA3, GABPB1, ETV4, and ZNF444) and five chromatin modifiers (SMC3, KDMA1, EZH2, RAD21, and CHD7). Interestingly, these 12 genes were found to be overexpressed in BCa patients. Further, C19MC targeted 42 tumor suppressor (TS) genes that were downregulated, of which 15 were significantly correlated with patient survival. Our findings suggest that transcription factors and chromatin modifiers at the promoter region may regulate C19MC overexpression. The upregulated C19MC members, transcription regulators, and TS genes can be further exploited as potential diagnostic and prognostic indicators as well as for therapeutic management of BCa.© 2023. The Author(s).