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鼻咽癌放射抗性中miRNA-mRNA调控网络的构建与分析

Construction and analysis of miRNA-mRNA regulatory networks in the radioresistance of nasopharyngeal carcinoma.

作者信息

Zhao Houyu, Chang Aoshuang, Ling Junjun, Zhou Wei, Ye Huiping, Zhuo Xianlu

机构信息

Affiliated Hospital of Guizhou Medical University, Guiyang, 550004 China.

Southwest Hospital, Army Medical University, Chongqing, 400037 China.

出版信息

3 Biotech. 2020 Dec;10(12):511. doi: 10.1007/s13205-020-02504-x. Epub 2020 Nov 7.

Abstract

Radiotherapy has been the major treatment strategy for nasopharyngeal carcinoma (NPC), while the occurrence of radioresistance may lead to cancer recurrence or progression. This study aimed to identify the key microRNAs (miRNAs) and their target genes in the development of NPC radioresistance. Public microarray data were searched and analyzed to screen the differentially expressed miRNAs (DEMs) and genes (DEGs) between radioresistant and radiosensitive NPC samples. MiRNA-mRNA networks were constructed. As a result, 5 DEMs and 195 DEGs were screened out. The DEGs were enriched in various signaling pathways, such as Cytokine-cytokine receptor interaction, Jak-STAT signaling pathway, and Toll-like receptor signaling pathway. Several hub genes, such as IGF2, OLA1, BBS10, MMP9, and BBS7 were identified. A regulatory miRNA-mRNA network containing 87 miRNA-mRNA pairs was constructed. Then, 14 key miRNA-mRNA pairs that contained the hub genes were further filtered out. In the networks, miR-203a-3p had the largest number of target genes. Afterwards, the candidate pairs (miR-203a-3p/BTK and miR-484/OLA1) have been verified by a qRT-PCR assay. In summary, we identified several miRNAs and hub genes via big data screening. A total of 87 miRNA-mRNA pairs (including 14 key pairs) were predicted to play a crucial role in the development of NPC radioresistance. These data provide a bioinformatics basis for further exploring the molecular mechanism of radiotherapy resistance in NPC. Future studies are needed to validate the results.

摘要

放射治疗一直是鼻咽癌(NPC)的主要治疗策略,而放射抗性的出现可能导致癌症复发或进展。本研究旨在确定鼻咽癌放射抗性发展过程中的关键微小RNA(miRNA)及其靶基因。通过搜索和分析公共微阵列数据,筛选出放射抗性和放射敏感的鼻咽癌样本之间差异表达的miRNA(DEM)和基因(DEG)。构建了miRNA-mRNA网络。结果,筛选出5个DEM和195个DEG。这些DEG富集于多种信号通路,如细胞因子-细胞因子受体相互作用、Jak-STAT信号通路和Toll样受体信号通路。鉴定出了几个枢纽基因,如IGF2、OLA1、BBS10、MMP9和BBS7。构建了一个包含87个miRNA-mRNA对的调控miRNA-mRNA网络。然后,进一步筛选出包含枢纽基因的14个关键miRNA-mRNA对。在这些网络中,miR-203a-3p的靶基因数量最多。随后,通过qRT-PCR分析验证了候选对(miR-203a-3p/BTK和miR-484/OLA1)。总之,我们通过大数据筛选鉴定出了几个miRNA和枢纽基因。总共预测有87个miRNA-mRNA对(包括14个关键对)在鼻咽癌放射抗性的发展中起关键作用。这些数据为进一步探索鼻咽癌放射抗性的分子机制提供了生物信息学基础。未来的研究需要验证这些结果。

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