Department of Clinical and Molecular Sciences, Università Politecnica Delle Marche, Via Tronto 10/A, 60126 Ancona, Italy.
Department of Biomolecular Sciences, University of Urbino Carlo Bo, 61029 Urbino, Italy.
Int J Mol Sci. 2023 Mar 7;24(6):5123. doi: 10.3390/ijms24065123.
The nuclear factor NF-kB is the master transcription factor in the inflammatory process by modulating the expression of pro-inflammatory genes. However, an additional level of complexity is the ability to promote the transcriptional activation of post-transcriptional modulators of gene expression as non-coding RNA (i.e., miRNAs). While NF-kB's role in inflammation-associated gene expression has been extensively investigated, the interplay between NF-kB and genes coding for miRNAs still deserves investigation. To identify miRNAs with potential NF-kB binding sites in their transcription start site, we predicted miRNA promoters by an in silico analysis using the PROmiRNA software, which allowed us to score the genomic region's propensity to be miRNA cis-regulatory elements. A list of 722 human miRNAs was generated, of which 399 were expressed in at least one tissue involved in the inflammatory processes. The selection of "high-confidence" hairpins in miRbase identified 68 mature miRNAs, most of them previously identified as inflammamiRs. The identification of targeted pathways/diseases highlighted their involvement in the most common age-related diseases. Overall, our results reinforce the hypothesis that persistent activation of NF-kB could unbalance the transcription of specific inflammamiRNAs. The identification of such miRNAs could be of diagnostic/prognostic/therapeutic relevance for the most common inflammatory-related and age-related diseases.
核因子 NF-κB 是炎症过程中的主要转录因子，通过调节促炎基因的表达。然而，其能够促进非编码 RNA（即 miRNAs）等转录后基因表达调节剂的转录激活，这增加了其复杂性。虽然 NF-κB 在炎症相关基因表达中的作用已经得到了广泛的研究，但 NF-κB 与编码 miRNA 的基因之间的相互作用仍值得研究。为了鉴定其转录起始位点具有潜在 NF-κB 结合位点的 miRNA，我们使用 PROmiRNA 软件进行了计算机分析，预测了 miRNA 启动子，该软件可以对基因组区域作为 miRNA 顺式调控元件的倾向进行评分。生成了 722 个人类 miRNA 的列表，其中 399 个在至少一种参与炎症过程的组织中表达。在 miRBase 中选择“高可信度”发夹，鉴定出 68 个成熟 miRNA，其中大多数先前被鉴定为炎症 miRNA。靶向途径/疾病的鉴定强调了它们与最常见的与年龄相关疾病的关系。总的来说，我们的结果支持这样的假设，即 NF-κB 的持续激活可能会使特定的炎症 miRNA 的转录失衡。这些 miRNA 的鉴定可能对最常见的炎症相关和年龄相关疾病具有诊断、预后和治疗意义。
