Institute of Pathology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Studničkova 2, 12800, Prague 2, Czech Republic.
Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital in Prague, Kateřinská 32, 121 08, Prague 2, Czech Republic.
Sci Rep. 2022 Jan 7;12(1):199. doi: 10.1038/s41598-021-03989-z.
Hepatocyte nuclear factor-1-beta (HNF1B) is a transcription factor and putative biomarker of solid tumours. Recently, we have revealed a variety of HNF1B mRNA alternative splicing variants (ASVs) with unknown, but potentially regulatory, functions. The aim of our work was to quantify the most common variants and compare their expression in tumour and non-tumour tissues of the large intestine, prostate, and kidney. The HNF1B mRNA variants 3p, Δ7, Δ7-8, and Δ8 were expressed across all the analysed tissues in 28.2-33.5%, 1.5-2%, 0.8-1.7%, and 2.3-6.9% of overall HNF1B mRNA expression, respectively, and occurred individually or in combination. The quantitative changes of ASVs between tumour and non-tumour tissue were observed for the large intestine (3p, Δ7-8), prostate (3p), and kidney samples (Δ7). Decreased expression of the overall HNF1B mRNA in the large intestine and prostate cancer samples compared with the corresponding non-tumour samples was observed (p = 0.019 and p = 0.047, respectively). The decreased mRNA expression correlated with decreased protein expression in large intestine carcinomas (p < 0.001). The qualitative and quantitative pattern of the ASVs studied by droplet digital PCR was confirmed by next-generation sequencing, which suggests the significance of the NGS approach for further massive evaluation of the splicing patterns in a variety of genes.
肝细胞核因子-1-β（HNF1B）是一种转录因子，也是实体瘤的潜在生物标志物。最近，我们发现了多种具有未知但可能具有调节功能的 HNF1B mRNA 可变剪接变体（ASVs）。我们的工作目的是定量分析最常见的变体，并比较它们在大肠、前列腺和肾脏肿瘤组织和非肿瘤组织中的表达。在分析的所有组织中，HNF1B mRNA 变体 3p、Δ7、Δ7-8 和 Δ8 的表达水平分别为总 HNF1B mRNA 表达量的 28.2-33.5%、1.5-2%、0.8-1.7%和 2.3-6.9%，并且单独或组合出现。在大肠（3p、Δ7-8）、前列腺（3p）和肾脏样本（Δ7）中观察到肿瘤和非肿瘤组织之间 ASVs 的定量变化。与相应的非肿瘤样本相比，大肠和前列腺癌样本中总 HNF1B mRNA 的表达降低（p=0.019 和 p=0.047）。大肠腺癌中 mRNA 表达的降低与蛋白表达的降低相关（p<0.001）。通过数字液滴 PCR 研究的 ASVs 的定性和定量模式通过下一代测序得到了证实，这表明 NGS 方法对于进一步大规模评估各种基因的剪接模式具有重要意义。
