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鉴定与喉鳞状细胞癌进展和不良预后相关的下调 CRNN。

Identification of Down-Expressed CRNN Associated with Cancer Progression and Poor Prognosis in Laryngeal Squamous Cell Carcinoma.

机构信息

Department of Otolaryngology, Hangzhou Hospital of Zhejiang Medical and Health Group, 310022 Hangzhou, Zhejiang, China.

Department of Otolaryngology, Chengdu First People's Hospital, 610000 Chengdu, Sichuan, China.

出版信息

Front Biosci (Landmark Ed). 2024 Mar 22;29(3):125. doi: 10.31083/j.fbl2903125.

DOI:10.31083/j.fbl2903125
PMID:38538265
Abstract

BACKGROUND

The prevalence of laryngeal squamous cell carcinoma (LSCC) is increasing, and it poses a significant threat to human health; therefore, identifying specific targets for LSCC remains crucial.

METHODS

Bioinformatics analysis was used to compare the different expression genes expressed in LSCC. Immunohistochemical assay and western blotting were used to analysis protein expression. Cell viability was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide)((4,5 Dimethyl thiazol-2-Yl)-2,5-Diphenyltetrazolium Bromide)4,5 Dimethyl thiazol-2-Yl)-2,5-Diphenyltetrazolium Bromide (MTT) and 5-ethynyl 2'-deoxyuridine (Edu) assay. Flow cytometry was used to measure the cell cycle. Cell migration was measured by wound healing assay and transwell assay.

RESULTS

Our analysis revealed 36 upregulated and 65 downregulated differentially expressed genes (DEGs) when comparing LSCC tumors to adjacent tissues, with cornulin (CRNN) identified as a key hub gene connecting these DEGs. We observed a consistent downregulation of CRNN expression in LSCC cell lines and tissues and was associated with poor patient survival and the tumor microenvironment. CRNN overexpression was found to significantly inhibit cell growth, cell cycle progression, migration and invasion, while CRNN knockdown had the opposite effects. Additionally, experiments demonstrated that CRNN overexpression suppressed tumor growth in nude mice.

CONCLUSIONS

CRNN functions as a potential tumor suppressor and regulates important aspects of LSCC, providing valuable insights into the role of CRNN in LSCC pathogenesis and potential for targeted therapeutic interventions.

摘要

背景

喉鳞状细胞癌(LSCC)的患病率正在增加,对人类健康构成重大威胁;因此,确定 LSCC 的特定靶点仍然至关重要。

方法

使用生物信息学分析比较 LSCC 中表达不同的差异表达基因。免疫组织化学检测和 Western blot 用于分析蛋白表达。通过 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基-2H-四唑溴盐((4,5-二甲基噻唑-2-基)-2,5-二苯基四唑溴盐)4,5-二甲基噻唑-2-基)-2,5-二苯基四唑溴盐(MTT)和 5-乙炔基 2'-脱氧尿苷(Edu)测定法测量细胞活力。流式细胞术用于测量细胞周期。通过划痕愈合试验和 Transwell 试验测量细胞迁移。

结果

我们的分析表明,将 LSCC 肿瘤与相邻组织进行比较时,有 36 个上调和 65 个下调的差异表达基因(DEGs),其中角蛋白聚糖(CRNN)被确定为连接这些 DEGs 的关键枢纽基因。我们观察到 LSCC 细胞系和组织中 CRNN 表达一致下调,与患者生存不良和肿瘤微环境相关。发现 CRNN 过表达可显著抑制细胞生长、细胞周期进程、迁移和侵袭,而 CRNN 敲低则产生相反的效果。此外,实验表明 CRNN 过表达可抑制裸鼠肿瘤生长。

结论

CRNN 作为一种潜在的肿瘤抑制因子发挥作用,调节 LSCC 的重要方面,为 CRNN 在 LSCC 发病机制中的作用以及潜在的靶向治疗干预提供了有价值的见解。

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