| 岳小乔,白琛俊,谢达菲,刘晓丹,周平坤.α粒子辐射诱发人支气管上皮BEP2D细胞癌变的snoRNA鉴定及靶标预测[J].中华放射医学与防护杂志,2020,40(6):413-419 |
| α粒子辐射诱发人支气管上皮BEP2D细胞癌变的snoRNA鉴定及靶标预测 |
| Identification and targets prediction of snoRNAs in α-particle induced carcinogenesis of human branchial epithelial cells |
| 投稿时间：2020-01-28 |
| DOI：10.3760/cma.j.issn.0254-5098.2020.06.001 |
| 中文关键词: α粒子 电离辐射 snoRNA sno116-14 癌变 |
| 英文关键词:α-particles Ionizing radiation snoRNA sno116-14 Cancerous |
| 基金项目:国家自然科学基金（81530085，11705283）；湖南省研究生科研创新项目（CX20190779） |
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| 中文摘要: |
| 目的 识别鉴定α粒子辐射致人支气管上皮BEP2D细胞癌变中的差异表达核仁小分子RNA（snoRNA），预测其靶标基因及RNA共表达网络。方法 通过全基因组转录组微阵列芯片对人支气管上皮细胞BEP2D及由其衍生的α粒子诱发癌变的BERP35T-4细胞的RNA差异表达谱分析，从中筛选出差异表达的snoRNA，qRT-PCR验证包括其衍生sdRNA在内的表达变化，通过生物信息学分析snoRNA的功能区，预测靶标和共表达网络。结果 qRT-PCR验证结果与芯片结果一致，sno116家族在BERP35T-4中表达下降，是BEP2D的0.105%，差异有统计学意义（t=26.60，P<0.01）；筛选的sno116-14等在癌变细胞BERP35T-4及人肺癌细胞A549和H1299等中表达量普遍下调，并且还发现sno116-14衍生的sdRNA的表达量在同一细胞中差异显著，建立了sno116家族的mRNA-lncRNA共表达网络，预测靶标有ZNF280D、TFDP1、CCDC28B、RPS6KA3、CANX、RUNX1、KALRN等，功能上与细胞增殖、细胞骨架结构等相关。结论 识别鉴定了α粒子辐射致细胞癌变相关差异表达snoRNA，预测sno116-14的靶标基因参与细胞增殖、细胞骨架结构等生物学过程和功能调控信号通路，为C/D box snoRNA发挥功能的作用方式及电离辐射致癌机制提供了新的信息。 |
| 英文摘要: |
| Objective To identify the differentially expressed snoRNAs in the carcinogenesis of cells induced by α-particles radiation and predict the targeted genes and RNA-co-expression networks. Methods Full transcriptome expression microarray biochips were employed to screen the differentially expressed snoRNAs between human bronchial epithelial BEP2D cell line and its derivative malignantly transformed cell line BERP35T-4 established by α-particle irradiation. The expression changes of snoRNAs and their derived sdRNAs were confirmed by qRT-PCR. The functional domains, targets and co-expression networks of snoRNA were predicted by bioinformatics analysis. Results Consistent with the result of microarray assay, the expression changes of the screened snoRNAs were confirmed by qRT-PCR. The expressions of sno116 family decreased in BERP35T-4, which was 0.105% (t=26.60, P<0.01) of BEP2D, and they were generally down-regulated in radiation-induced carcinogenic BERP35T-4 cells and the human lung cancer cell lines A549 and H1299. It was also found that the expression level of the sdRNAs derived from sno116-14 was significantly different in the same cells. It was speculated that these less expressed sdRNAs of sno116-14 could be due to degradation as the consequence of interaction with their targets. The co-expression networks of sno116 family with other types of RNA were established, and the predicted targets of sno116-14 included ZNF280D, TFDP1, CCDC28B, RPS6KA3, CANX, RUNX1 and KALRN, which were related to the functions of cell proliferation and cytoskeletal structure. Conclusions Some differentially expressed snoRNAs related to α-particle induced carcinogenesis have been identified. It is predicted that the target gene of sno116-14 is involved in the biological processes such as cell proliferation, cytoskeletal structure and the signaling pathways for function regulation, providing new information for the function model of C/D box snoRNAs and the mechanism of radiation carcinogenesis. |
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