MicroRNAs (miRNAs) are short (20–24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. One of the miRNAs that has been shown to play a role in various pathologies like cancer, neurological disorders and cardiovascular diseases is miRNA-26b. However, these studies only demonstrated rather ambiguous associations without revealing a causal relationship. Therefore, the aim of this study is to establish and validate a mouse model which enables the elucidation of the exact role of miRNA-26b in various pathologies. A miRNA-26b-deficient mouse model was established using homologous recombination and validated using PCR. miRNA-26b-deficient mice did not show any physiological abnormalities and no effects on systemic lipid levels, blood parameters or tissue leukocytes. Using next generation sequencing, the gene expression patterns in miRNA-26b-deficient mice were analyzed and compared to wild type controls. This supported the already suggested role of miRNA-26b in cancer and neurological processes, but also revealed novel associations of miRNA-26b with thermogenesis and allergic reactions. In addition, detailed analysis identified several genes that seem to be highly regulated by miRNA-26b, which are linked to the same pathological conditions, further confirming the role of miRNA-26b in these pathologies and providing a strong validation of our mouse model. miRNA-26b plays an important role in various pathologies, although causal relationships still have to be established. The described mouse model of miRNA-26b deficiency is a crucial first step towards the identification of the exact role of miRNA-26b in various diseases that could identify miRNA-26b as a promising novel diagnostic or even therapeutic target in a broad range of pathologies.

中文翻译：

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miRNA-26b KO 小鼠模型的转录组特征提示新靶点

MicroRNA (miRNA) 是短的 (20–24 nt) 非编码 RNA，通过影响 mRNA 的稳定性和翻译参与多细胞生物中基因表达的转录后调控。已证明在癌症、神经系统疾病和心血管疾病等各种病理中发挥作用的 miRNA 之一是 miRNA-26b。然而，这些研究只证明了相当模糊的关联，而没有揭示因果关系。因此，本研究的目的是建立和验证一种小鼠模型，该模型能够阐明 miRNA-26b 在各种病理中的确切作用。使用同源重组建立 miRNA-26b 缺陷小鼠模型并使用 PCR 进行验证。miRNA-26b 缺陷小鼠没有表现出任何生理异常并且对全身脂质水平没有影响，血液参数或组织白细胞。使用下一代测序，分析了 miRNA-26b 缺陷小鼠的基因表达模式，并与野生型对照进行了比较。这支持了已经提出的 miRNA-26b 在癌症和神经过程中的作用，但也揭示了 miRNA-26b 与产热和过敏反应的新关联。此外，详细分析确定了几个似乎受 miRNA-26b 高度调节的基因，这些基因与相同的病理条件相关，进一步证实了 miRNA-26b 在这些病理中的作用，并为我们的小鼠模型提供了强有力的验证。miRNA-26b 在各种病理中发挥着重要作用，尽管仍然需要建立因果关系。