KLF15 转录激活速激肽前体 1 诱导头颈部鳞状细胞癌的神经周围侵袭

IF 1.6 4区 医学 Q4 BIOCHEMICAL RESEARCH METHODS Combinatorial chemistry & high throughput screening Pub Date : 2024-10-14 DOI:10.2174/0113862073331908241002044719
Yupeng Shen, Yong Shi, Xin Liu, Ming Zhang, Liang Zhou, Chengzhi Xu
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引用次数: 0

摘要

研究目的本研究旨在确定头颈部鳞状细胞癌(HNSCC)中与外周神经侵犯(PNI)相关的新型生物标记物:方法:通过鉴定 HNSCC 中与 PNI 相关的差异表达 mRNA(DE-mRNA),构建 PNI 相关风险评分模型。计算了Tachykinin Precursor 1(TAC1)的表达水平和ROC曲线。此外,还建立了两种 PNI 体外模型进行研究,包括 Matrigel-PNI 模型和 Transwell-PNI 模型。此外,还通过 qRTPCR 预测并验证了 TAC1 的转录因子:结果:在 PNI 阳性组和阴性组 HNSCC 患者中共鉴定出 139 个 DE-mRNAs 。建立了包含 20 个与 PNI 相关的 DE-mRNA 的风险分数标记模型。TAC1被鉴定为潜在的高表达PNI标志物,在预测PNI事件方面表现良好。与 TAC1 表达量较低的 HNSCC 患者相比,TAC1 表达量较高的患者生存率明显较低。此外,根据 Matrigel-PNI 模型和 Transwell-PNI 模型,体外敲除 TAC1 能明显抑制 HNSCC 细胞的神经侵袭。此外,还预测并验证了KLF15是HNSCC中TAC1的转录激活因子:本研究强调了 KLF15 对 TAC1 转录的激活促进了 HNSCC 细胞中的 PNI,这为 HNSCC 细胞中 PNI 的分子诊断提供了指导。
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KLF15 Transcription Activated Tachykinin Precursor 1 to Induce Perineural Invasion in Head and Neck Squamous Cell Carcinoma.

Objective: In this study, we aimed to identify novel biomarkers related to Peripheral Neural Invasion (PNI) in head and neck squamous cell carcinoma (HNSCC).

Methods: The PNI-related differentially expressed mRNAs (DE-mRNAs) in HNSCC were identified to construct a PNI-related risk score model. The expression level and ROC curve for Tachykinin Precursor 1 (TAC1) were calculated. Additionally, two kinds of in vitro models of PNI were established for investigation, including the Matrigel-PNI model and the Transwell-PNI model. Furthermore, the transcription factor of the TAC1 was predicted and verified by qRTPCR.

Results: A total of 139 DE-mRNAs were identified in PNI positive and negative groups of HNSCC patients. The risk-score marker model incorporating 20 PNI-related DE-mRNAs was established. The TAC1 was identified as a potential highly expressed PNI marker, which exhibited good performance in predicting PNI events. Patients with higher TAC1 expressions demonstrated significantly shorter survival rates compared to those with lower TAC1 expressions in HNSCC. Besides, the knockdown of TAC1 significantly repressed neural invasion in HNSCC cells in vitro, according to the Matrigel-PNI model and Transwell-PNI model. Furthermore, KLF15 was predicted and verified as a transcription activator of TAC1 in HNSCC.

Conclusion: This study highlights that the activation of KLF15 transcription of TAC1 promotes PNI in HNSCC cells, which provides guidance regarding the molecular diagnosis of PNI in HNSCC cells.

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来源期刊
CiteScore
3.10
自引率
5.60%
发文量
327
审稿时长
7.5 months
期刊介绍: Combinatorial Chemistry & High Throughput Screening (CCHTS) publishes full length original research articles and reviews/mini-reviews dealing with various topics related to chemical biology (High Throughput Screening, Combinatorial Chemistry, Chemoinformatics, Laboratory Automation and Compound management) in advancing drug discovery research. Original research articles and reviews in the following areas are of special interest to the readers of this journal: Target identification and validation Assay design, development, miniaturization and comparison High throughput/high content/in silico screening and associated technologies Label-free detection technologies and applications Stem cell technologies Biomarkers ADMET/PK/PD methodologies and screening Probe discovery and development, hit to lead optimization Combinatorial chemistry (e.g. small molecules, peptide, nucleic acid or phage display libraries) Chemical library design and chemical diversity Chemo/bio-informatics, data mining Compound management Pharmacognosy Natural Products Research (Chemistry, Biology and Pharmacology of Natural Products) Natural Product Analytical Studies Bipharmaceutical studies of Natural products Drug repurposing Data management and statistical analysis Laboratory automation, robotics, microfluidics, signal detection technologies Current & Future Institutional Research Profile Technology transfer, legal and licensing issues Patents.
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