对鼻咽癌中与基因表达相关的ceRNA网络和DNA甲基化的揭示
Uncovering the ceRNA network and DNA methylation associated with gene expression in nasopharyngeal carcinoma.
发表日期:2023 Sep 14
作者:
Ting Zhang, Lu Pei, Wen-Li Qiu, Yu-Xia Wei, Bi-Yun Liao, Feng-Lian Yang
来源:
Epigenetics & Chromatin
摘要:
本研究旨在揭示通过竞争性内源性RNA(ceRNA)和DNA甲基化调节的异常表达基因在鼻咽癌中的表达情况,并验证ceRNA网络中长链非编码RNA(lncRNA)在鼻咽癌进展中的作用。我们基于GSE64634(mRNA)、GSE32960(miRNA)、GSE95166(lncRNA)和GSE126683(lncRNA)数据集,筛选了鼻咽癌中差异表达的mRNA、miRNA和lncRNA。随后构建了ceRNA网络。利用GSE62336数据集筛选了甲基化差异基因。鉴定了同时受到ceRNA网络和DNA甲基化调节的异常表达基因。在ceRNA网络中,通过RT-qPCR验证了RP11-545G3.1 lncRNA在鼻咽癌组织和细胞中的表达。在RP11-545G3.1敲低后,通过CCK-8、划痕愈合和转移试验评估了CNE-2和NP69细胞的存活性、迁移和侵袭性。
本研究鉴定了鼻咽癌组织中异常表达的mRNA、miRNA和lncRNA。构建了一个包含3个lncRNA、15个miRNA和129个mRNA的ceRNA网络。基于ceRNA网络中的mRNA构建了蛋白相互作用网络(PPI网络)的节点,进一步评估了HMGA1与鼻咽癌的总体生存和无病生存的相关性。我们筛选出2个由ceRNA网络和低甲基化调节的上调基因以及26个由ceRNA网络和高甲基化调节的下调基因。RP11-545G3.1在鼻咽癌组织和细胞中高表达。此外,RP11-545G3.1的敲低降低了CNE-2和NP69细胞的存活性、迁移和侵袭性。
我们的研究揭示了鼻咽癌的表观遗传调控,并确定了RP11-545G3.1对鼻咽癌进展的影响。© 2023. BioMed Central Ltd., part of Springer Nature.
This study aimed to uncover abnormally expressed genes regulated by competitive endogenous RNA (ceRNA) and DNA methylation nasopharyngeal carcinoma and to validate the role of lncRNAs in the ceRNA network on nasopharyngeal carcinoma progression.Based on the GSE64634 (mRNA), GSE32960 (miRNA), GSE95166 (lncRNA), and GSE126683 (lncRNA) datasets, we screened differentially expressed mRNAs, miRNAs and lncRNAs in nasopharyngeal carcinoma. A ceRNA network was subsequently constructed. Differentially methylated genes were screened using the GSE62336 dataset. The abnormally expressed genes regulated by both the ceRNA network and DNA methylation were identified. In the ceRNA network, the expression of RP11-545G3.1 lncRNA was validated in nasopharyngeal carcinoma tissues and cells by RT-qPCR. After a knockdown of RP11-545G3.1, the viability, migration, and invasion of CNE-2 and NP69 cells was assessed by CCK-8, wound healing and Transwell assays.This study identified abnormally expressed mRNAs, miRNAs and lncRNAs in nasopharyngeal carcinoma tissues. A ceRNA network was constructed, which contained three lncRNAs, 15 miRNAs and 129 mRNAs. Among the nodes in the PPI network based on the mRNAs in the ceRNA network, HMGA1 was assessed in relation to the overall and disease-free survival of nasopharyngeal carcinoma. We screened two up-regulated genes regulated by the ceRNA network and hypomethylation and 26 down-regulated genes regulated by the ceRNA network and hypermethylation. RP11-545G3.1 was highly expressed in the nasopharyngeal carcinoma tissues and cells. Moreover, the knockdown of RP11-545G3.1 reduced the viability, migration, and invasion of CNE-2 and NP69 cells.Our findings uncovered the epigenetic regulation in nasopharyngeal carcinoma and identified the implications of RP11-545G3.1 on the progression of nasopharyngeal carcinoma.© 2023. BioMed Central Ltd., part of Springer Nature.