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低背景环境下高分化喉鳞状细胞癌细胞的转录组分析

Transcriptome analysis of well-differentiated laryngeal squamous cell carcinoma cells in below-background environment.

作者信息

Liu Yilin, Gao Yuzhu, Cheng Jiahan, Ma Tengfei, Xie Yike, Wen Qiao, Yuan Zimu, Wang Ling, Cheng Juan, Wu Jiang, Zou Jian, Liu Jifeng, Gao Mingzhong, Li Weimin, Xie Heping

机构信息

Deep Underground Space Medical Center, West China Hospital, Sichuan University, Chengdu, China.

Department of Ophthalmology, West China Hospital, Sichuan University, Chengdu, China.

出版信息

Ann Transl Med. 2022 Aug;10(15):824. doi: 10.21037/atm-22-2997.

Abstract

BACKGROUND

Preliminary research has shown an inhibited growth rate of well-differentiated laryngeal squamous cell carcinoma cells (FD-LSC-1) in below-background radiation (BBR), but how the cells respond to this environmental stress and the potential mechanisms are yet unknown. The current study aimed to reveal the molecular differences in cells grown under BBR conditions and normal radiation at the transcriptional level.

METHODS

The expression profiles between FD-LSC-1 cells grown in a deep underground laboratory and above ground laboratory collected on day 4 were investigated by whole-transcriptome analysis, including messenger RNAs (mRNAs), long non-coding RNAs (lncRNAs), circular RNAs (circRNAs), and microRNAs (miRNAs). Functional analyses of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were then implemented for differentially expressed (DE) mRNAs and target genes of lncRNAs and circRNAs. Co-expression levels and the Bayesian network of DE genes were subsequently constructed, and the reliability of expression patterns were validated by quantitative real-time polymerase chain reaction (PCR).

RESULTS

The study identified a total of 671 mRNAs, 286 lncRNAs, 489 circRNAs, and 6 miRNAs as significantly expressed in response to the environmental stress. The GO annotations regarding the biological processes category were mainly biological regulation, metabolic process, response to stimulus, cell cycle, and modification process. The KEGG enrichment analysis indicated that TGF-β and Hippo signaling played a crucial role in the transcriptional regulation of FD-LSC-1 cell growth under background radiation. Further network construction suggested that the enriched KEGG pathways affected this process by regulating cell proliferation-related genes including , , , , and .

CONCLUSIONS

Below-background radiation can lead to transcriptional changes in FD-LSC-1 cells cultured in the deep underground. The inhibitory growth effect is associated with multiple biological processes as well as canonical pathways of proliferation.

摘要

背景

初步研究表明,在低于本底辐射(BBR)条件下,高分化喉鳞状细胞癌细胞(FD-LSC-1)的生长速率受到抑制,但细胞如何应对这种环境应激及其潜在机制尚不清楚。当前研究旨在揭示在BBR条件下生长的细胞与正常辐射条件下生长的细胞在转录水平上的分子差异。

方法

通过全转录组分析,研究了在地下深层实验室和地面实验室中培养4天后收集的FD-LSC-1细胞之间的表达谱,包括信使核糖核酸(mRNA)、长链非编码核糖核酸(lncRNA)、环状核糖核酸(circRNA)和微小核糖核酸(miRNA)。然后对差异表达(DE)的mRNA以及lncRNA和circRNA的靶基因进行基因本体论(GO)功能分析和京都基因与基因组百科全书(KEGG)通路富集分析。随后构建DE基因的共表达水平和贝叶斯网络,并通过定量实时聚合酶链反应(PCR)验证表达模式的可靠性。

结果

该研究共鉴定出671种mRNA、286种lncRNA、489种circRNA和6种miRNA在应对环境应激时显著表达。关于生物过程类别的GO注释主要为生物调控、代谢过程、对刺激的反应、细胞周期和修饰过程。KEGG富集分析表明,转化生长因子-β(TGF-β)和Hippo信号通路在本底辐射下FD-LSC-1细胞生长的转录调控中起关键作用。进一步的网络构建表明,富集的KEGG通路通过调节包括 、 、 、 和 在内的细胞增殖相关基因来影响这一过程。

结论

低于本底辐射可导致在地下深层培养的FD-LSC-1细胞发生转录变化。生长抑制效应与多种生物学过程以及增殖的经典通路有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6010/9403920/7d4331f19af9/atm-10-15-824-f1.jpg

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