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Comprehensive quantitative analysis of alternative splicing variants reveals the HNF1B mRNA splicing pattern in various tumour and non-tumour tissues.

ABSTRACT: 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.

SUBMITTER: Hojny J

PROVIDER: S-EPMC8741901 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature

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Comprehensive quantitative analysis of alternative splicing variants reveals the HNF1B mRNA splicing pattern in various tumour and non-tumour tissues.

Hojny Jan J Michalkova Romana R Krkavcova Eva E Bui Quang Hiep QH Bartu Michaela M Nemejcova Kristyna K Kalousova Marta M Kleiblova Petra P Dundr Pavel P Struzinska Ivana I

Scientific reports 20220107 1

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 analyse ...[more]

PMID: 34997048

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Project description:Despite the scientific relevance of circular RNAs (circRNAs), the study of these RNAs in non-model organisms, especially in sheep, is still in its infancy. On the other hand, while some studies have focused on sheep circRNA identification in a limited number of tissues, there is a lack of comprehensive analysis that profile circRNA expression patterns across the tissues not yet investigated. In this study, 61 public RNA sequencing datasets from 12 different tissues were uniformly analyzed to identify circRNAs, profile their expression and investigate their various characteristics. We reported for the first time a circRNA expression landscape with functional annotation in sheep tissues not yet investigated including hippocampus, BonMarrowMacrophage, left-ventricle, thymus, ileum, reticulum and 23-day-embryo. A stringent computational pipeline was employed and 8919 exon-derived circRNAs with high confidence were identified, including 88 novel circRNAs. Tissue-specificity analysis revealed that 3059 circRNAs were tissue-specific, which were also more specific to the tissues than linear RNAs. The highest number of tissue-specific circRNAs was found in kidney, hippocampus and thymus, respectively. Co-expression analysis revealed that expression of circRNAs may not be affected by their host genes. While most of the host genes produced more than one isoform, only one isoform had dominant expression across the tissues. The host genes of the tissue-specific circRNAs were significantly enriched in biological/pathways terms linked to the important functions of their corresponding tissues, suggesting potential roles of circRNAs in modulating physiological activity of those tissues. Interestingly, functional terms related to the regulation and various signaling pathways were significantly enriched in all tissues, suggesting some common regulatory mechanisms of circRNAs to modulate the physiological functions of tissues. Finding of the present study provide a valuable resource for depicting the complexity of circRNAs expression across tissues of sheep, which can be useful for the field of sheep genomic and veterinary research.

Dataset Information

Comprehensive quantitative analysis of alternative splicing variants reveals the HNF1B mRNA splicing pattern in various tumour and non-tumour tissues.

Publications

Comprehensive quantitative analysis of alternative splicing variants reveals the HNF1B mRNA splicing pattern in various tumour and non-tumour tissues.

Similar Datasets

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