ZFAS1 lncRNA 在头颈部鳞状细胞癌中的致癌作用。

Oncogenic Role of ZFAS1 lncRNA in Head and Neck Squamous Cell Carcinomas.

机构信息

Department of Cancer Immunology, Chair of Medical Biotechnology, Poznan University of Medical Sciences, 8 Rokietnicka Street, 60-806 Poznan, Poland.

Laboratory of Cancer Genetics, Greater Poland Cancer Centre, 15 Garbary Street, Room 5025, 61-866 Poznan, Poland.

出版信息

Cells. 2019 Apr 21;8(4):366. doi: 10.3390/cells8040366.

DOI:10.3390/cells8040366

PMID:31010087

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6523746/

Abstract

BACKGROUND

Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous disease with high mortality. The identification of specific HNSCC biomarkers will increase treatment efficacy and limit the toxicity of current therapeutic strategies. Long non-coding RNAs (lncRNAs) are promising biomarkers. Accordingly, here we investigate the biological role of and its potential as a biomarker in HNSCC.

METHODS

The expression level of in HNSCC cell lines was analyzed using qRT-PCR. Based on the HNSCC TCGA data, the expression profile, clinicopathological features, and expression of correlated genes were analyzed in patient tissue samples. The selected genes were classified according to their biological function using the PANTHER tool. The interaction between lncRNA:miRNA and miRNA:mRNA was tested using available online tools. All statistical analyses were accomplished using GraphPad Prism 5.

RESULTS

The expression of was up-regulated in the metastatic FaDu cell line relative to the less aggressive SCC-25 and SCC-040 and dysplastic DOK cell lines. The TCGA data indicated an up-regulation of in HNSCCs compared to normal tissue samples. The levels typically differed depending on the cancer stage and T-stage. Patients with a lower expression of presented a slightly longer disease-free survival and overall survival. The analysis of genes associated with , as well its targets, indicate that they are linked with crucial cellular processes. In the group of patients with low expression of , we detected the up-regulation of suppressors and down-regulation of genes associated with epithelial-to-mesenchymal transition (EMT) process, metastases, and cancer-initiating cells. Moreover, the negative correlation between and its host gene, , was observed. The analysis of interactions indicated that has a binding sequence for . The expression of and is negatively correlated in HNSCC patients. can regulate the 3'UTR of mRNA. In the group of patients with high expression of and low expression of , we detected an up-regulation of .

CONCLUSIONS

In HNSCC, displays oncogenic properties, regulates important processes associated with EMT, cancer-initiating cells, and metastases, and might affect patients' clinical outcomes. likely regulates the cell phenotype through and its downstream targets. Following further validation, might prove a new and valuable biomarker.

摘要

背景

头颈部鳞状细胞癌（HNSCC）是一种具有高死亡率的异质性疾病。鉴定特定的 HNSCC 生物标志物将提高治疗效果，并限制当前治疗策略的毒性。长非编码 RNA（lncRNA）是很有前途的生物标志物。因此，在这里我们研究了在 HNSCC 中的生物学作用及其作为生物标志物的潜力。

方法

使用 qRT-PCR 分析 HNSCC 细胞系中的表达水平。根据 HNSCC TCGA 数据，在患者组织样本中分析的表达谱、临床病理特征和相关基因的表达。使用 PANTHER 工具根据其生物学功能对选定的基因进行分类。使用可用的在线工具测试 lncRNA:miRNA 和 miRNA:mRNA 之间的相互作用。所有统计分析均使用 GraphPad Prism 5 完成。

结果

与侵袭性较低的 SCC-25 和 SCC-040 以及发育不良的 DOK 细胞系相比，转移性 FaDu 细胞系中表达上调。TCGA 数据表明 HNSCC 与正常组织样本相比上调。的水平通常根据癌症阶段和 T 阶段而有所不同。表达较低的患者无病生存率和总生存率略长。与相关基因及其靶基因的分析表明，它们与关键的细胞过程有关。在表达较低的患者组中，我们检测到抑制物的上调和与上皮间质转化（EMT）过程、转移和癌症起始细胞相关的基因下调。此外，观察到与宿主基因的负相关。相互作用分析表明具有结合序列。在 HNSCC 患者中表达呈负相关。可以调节 mRNA 的 3'UTR。在表达和表达较低的患者组中，我们检测到的上调。