1α,25(OH)2D3在卵巢癌细胞SKOV-3中调控lncRNAs表达谱
1α,25(OH)2D3 regulates the expression profile of lncRNAs in the ovarian cancer cell line SKOV-3
目的:通过研究1α,25(OH)2D3对卵巢癌细胞内lncRNAs表达谱的影响,揭示维生素D抗肿瘤作用的新方向,丰富维生素D的非经典作用。方法:选用卵巢癌SKOV-3细胞,应用基因芯片技术,分析活性维生素D处理组与对照组的基因表达谱。通过与lncRNAs共表达的基因,运用Gene Ontology(GO)与KEGG数据库对差异表达的lncRNAs进行功能和通路分析,超几何分布检验方法得到与lncRNAs显著相关的转录因子。结果:通过基因芯片结果发现,与对照组相比,分别有139条与105条差异表达的lncRNAs和mRNAs。差异表达的lncRNAs参与多种与维生素D相关的信号通路,例如:系统性红斑狼疮,破骨细胞的分化等。并且参与多种肿瘤相关信号通路,包括:Wnt、TNF以及TGFβ受体信号通路等。差异表达的lncRNAs主要受TAF7、POU2F2和KAT2A这三个转录因子的调控。此外,与CYP24A1、CDH1和VDR共表达的lncRNAs有17个,这些lncRNAs共同参与EMT过程与VD信号通路。结论:本文首次探索了活性维生素D1α,25(OH)2D3在卵巢癌细胞中lncRNAs的基因表达谱,并为通过调控lncRNAs的表达从而研究1α,25(OH)2D3的抗肿瘤作用提供了基础。
Long non-coding RNAs (lncRNAs) have been reported to be involved in processes of tumor progression. 1α,25-dihydroxyvitamin D3 (1α,25(OH)2D3), the active form of vitamin D, has an anti-proliferative effect on tumor cells. Therefore, differentially expressed lncRNAs regulated by 1α,25(OH)2D3 may be associated with tumor progress. This study was aimed to investigate the lncRNAs profiling pattern regulated by 1α,25(OH)2D3 in ovarian cancer cell line SKOV-3 using microarray analysis. After 72 hours of 1α,25(OH)2D3 treatment, 139 lncRNAs and 105 mRNAs were significantly dysregulated. Five lncRNAs were validated by quantitative reverse transcription polymerase chain reaction (qRT-PCR). In functional analysis, dysregulated lncRNAs can participate in biological processes related to systemic lupus erythematosus, alcoholism, osteoclast differentiation and cancer signaling pathways, such as Wnt, TNF and TGF-β receptor signaling. The dysregulated lncRNAs were associated with their co-expressed genes and may be mainly regulated by these three transcription factors, TAF7, POU2F2 and KAT2A. Additionally, there were 17 lncRNAs co-expressed with genes VDR, CYP24A1 and CDH1, suggesting that these lncRNAs acted as the connection to associate vitamin D signaling with EMT. These data constitute the first report of lncRNA expression patterns regulated by 1α,25(OH)2D3 in human ovarian cancer cells, and will provide new evidence for the anti-tumor effect of 1α,25(OH)2D3 through lncRNAs.
薛雅琪、叶梦璇、王宋之、蒋菲、周光明、裴海龙、李冰燕、胡文涛
肿瘤学基础医学分子生物学
营养学长链非编码RNAs1α25(OH)2D3卵巢癌基因表达谱
lncRNAs1α25(OH)2D3ovarian cancerexpression profile
薛雅琪,叶梦璇,王宋之,蒋菲,周光明,裴海龙,李冰燕,胡文涛.1α,25(OH)2D3在卵巢癌细胞SKOV-3中调控lncRNAs表达谱[EB/OL].(2020-02-17)[2025-08-16].http://www.paper.edu.cn/releasepaper/content/202002-71.点此复制
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