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甲状腺乳头状癌中差异表达的微小RNA的研究与验证以及靶基因预测,特别关注自噬信号通路。

Investigation and confirmation of differentially expressed miRNAs, as well as target gene prediction in papillary thyroid cancer, with a special emphasis on the autophagy signaling pathway.

作者信息

Zehtabi Mojtaba, Akbarpour Zahra, Valizadeh Sepehr, Roosta Yousef, Khamaneh Amir Mahdi, Raeisi Mortaza

机构信息

Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.

Rahat Breathe and Sleep Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.

出版信息

Mol Biol Res Commun. 2022;11(4):173-181. doi: 10.22099/mbrc.2022.43844.1751.

Abstract

Papillary thyroid carcinoma (PTC) is the most common endocrine cancer. However, the role of biomechanics in the development and progression of PTC is obscure. The microarray dataset GSE104005 was examined to identify important microRNAs (miRNAs or miRs) and their probable roles in the carcinogenesis of PTC. The gene expression omnibus (GEO) database was used to obtain the data. R was used to access the differentially expressed miRNAs (DEMs) and genes (DEGs). The multiMiR software was used to predict DEM targets. To validate the top DEMs and DEGs, thirty tissue samples were obtained from PTC patients who had their thyroids removed and compared with 30 normal samples. The total RNA content of the tumor and corresponding non-tumoral adjacent samples were purified and converted to cDNA. Expression levels of top dysregulated miRNAs and their target and predicted DEG were evaluated using the RT-qPCR method. miR-182 and miR-183 were top upregulated miRs and miR-30d was the most downregulated miR among DEMs. Furthermore, FOXO1 which was shown to be targeted by aforementioned miRNAs, was the most downregulated genes among other DEGs. 10 hub nodes were detected by PPI construction. PTEN was the hub node with highest score. The i gene expression analysis was also showed the same expression pattern in tissues. Significant increase in miR-182-5p and miR-183-5p expressions, as well as a significant decrease in FOXO1 and miR-30d-5p expressions, suggest that PTC cells may tend to preserve their autophagy capability.

摘要

甲状腺乳头状癌(PTC)是最常见的内分泌癌。然而,生物力学在PTC发生发展中的作用尚不清楚。研究了基因芯片数据集GSE104005,以确定重要的微小RNA(miRNA或miR)及其在PTC致癌作用中的可能作用。利用基因表达综合数据库(GEO)获取数据。使用R语言来获取差异表达的miRNA(DEM)和基因(DEG)。使用multiMiR软件预测DEM的靶标。为了验证排名靠前的DEM和DEG,从接受甲状腺切除的PTC患者中获取了30个组织样本,并与30个正常样本进行比较。纯化肿瘤及相应非肿瘤相邻样本的总RNA含量,并将其转化为cDNA。使用RT-qPCR方法评估排名靠前的失调miRNA及其靶标和预测的DEG的表达水平。miR-182和miR-183是上调程度最高的miR,而miR-30d是DEM中下调程度最大的miR。此外,被上述miRNA靶向的FOXO1是其他DEG中下调程度最大的基因。通过蛋白质-蛋白质相互作用(PPI)构建检测到10个枢纽节点。PTEN是得分最高的枢纽节点。i基因表达分析在组织中也显示出相同的表达模式。miR-182-5p和miR-183-5p表达显著增加,以及FOXO1和miR-30d-5p表达显著降低,表明PTC细胞可能倾向于保留其自噬能力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/af52/9905749/c5450b4f5582/mbrc-11-173-g001.jpg

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