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差异表达的微小RNA,包括位于24号染色体上的一个大型微小RNA簇,与马的肉瘤样瘤和鳞状细胞癌相关。

Differentially expressed microRNAs, including a large microRNA cluster on chromosome 24, are associated with equine sarcoid and squamous cell carcinoma.

作者信息

Bogedale Kirsten, Jagannathan Vidhya, Gerber Vinzenz, Unger Lucia

机构信息

Department of Clinical Veterinary Medicine, Swiss Institute of Equine Medicine, Vetsuisse Faculty, University of Bern and Agroscope, Bern, Switzerland.

Department of Clinical Research and Veterinary Public Health, Institute of Genetics, Vetsuisse Faculty, University of Bern, Bern, Switzerland.

出版信息

Vet Comp Oncol. 2019 Jun;17(2):155-164. doi: 10.1111/vco.12458. Epub 2019 Feb 15.

Abstract

The aim of this study was to investigate microRNA (miRNA) differential expression in the two most common equine skin tumours, equine sarcoid (ES) and squamous cell carcinoma (SCC), and its potential influence on the tumour microenvironment at post-transcriptional level. We investigated miRNA fingerprints in four subgroups: mild (ESM) and aggressive (ESA) ES and ocular SCC (oSCC) and genital SCC (gSCC). Three tumours and three control samples were included in each of the four subgroups. Following next generation sequencing, miRNA differential expression analysis using DESeq2 was carried out. Pathways associated with the human mature homologues of identified dysregulated miRNAs were predicted using DIANA- miRPath v3.0. When comparing tumour vs control tissue, 57 miRNAs in ESM, six in ESA, 47 in oSCC and zero in gSCC were found to be differentially expressed and may thus serve as potential diagnostic tissue biomarkers. Whereas, ES lesions in general were associated with downregulation of the miR-200 family, which may trigger epithelial-mesenchymal transition, ESM lesions were associated with upregulation of the proposed tumour-suppressive miRNA cluster on equine chromosome 24. In contrast, the oSCC tumours showed downregulation of this cluster as well as downregulation of the miR-34 family, which may favour oSCC tumour cell metabolism. To further validate the proposed diagnostic miRNA fingerprints and their suggested biological effects, further miRNA studies need to be carried out in larger study cohorts.

摘要

本研究的目的是调查微小RNA(miRNA)在两种最常见的马皮肤肿瘤——马肉瘤(ES)和鳞状细胞癌(SCC)中的差异表达,及其在转录后水平对肿瘤微环境的潜在影响。我们调查了四个亚组中的miRNA指纹图谱:轻度(ESM)和侵袭性(ESA)的ES以及眼部SCC(oSCC)和生殖器SCC(gSCC)。四个亚组中的每一组都纳入了三个肿瘤样本和三个对照样本。在进行下一代测序后,使用DESeq2进行了miRNA差异表达分析。使用DIANA- miRPath v3.0预测了与已鉴定的失调miRNA的人类成熟同源物相关的通路。在比较肿瘤组织与对照组织时,发现ESM中有57个miRNA、ESA中有6个、oSCC中有47个、gSCC中没有差异表达,因此这些miRNA可能作为潜在的诊断组织生物标志物。一般来说,ES病变与miR-200家族的下调有关,这可能引发上皮-间质转化,而ESM病变与马24号染色体上拟议的肿瘤抑制miRNA簇的上调有关。相反,oSCC肿瘤显示该簇下调以及miR-34家族下调,这可能有利于oSCC肿瘤细胞的代谢。为了进一步验证所提出的诊断性miRNA指纹图谱及其推测的生物学效应,需要在更大的研究队列中开展进一步的miRNA研究。

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