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脯氨酰 4-羟化酶亚基 α3 通过调控上皮-间充质转化在头颈部鳞状细胞癌中发挥致癌作用。

Prolyl 4-hydroxylase subunit alpha 3 presents a cancer promotive function in head and neck squamous cell carcinoma via regulating epithelial-mesenchymal transition.

机构信息

Department of Otolaryngology, Gaomi People's Hospital, Weifang, Shandong, 261500, PR China.

Brain Hospital of Weifang, Shandong, 261000, PR China.

出版信息

Arch Oral Biol. 2020 May;113:104711. doi: 10.1016/j.archoralbio.2020.104711. Epub 2020 Mar 19.

DOI:10.1016/j.archoralbio.2020.104711
PMID:32220804
Abstract

OBJECTIVE

This study aimed to explore the prognostic value and functional role of Prolyl 4-Hydroxylase Subunit Alpha 3 (P4HA3) in head and neck squamous cell carcinoma.

METHODS

We downloaded the RNA-Seq dataset of head and neck squamous cell carcinoma for analyzing the expression of P4HA3 and determining its prognostic value. Head and neck squamous cell carcinoma cell lines CAL27 and FaDu were chose for gain- and loss-of-function of P4HA3 tests. mRNA and protein levels of P4HA3 in head and neck squamous cell carcinoma cells were tested by quantitative real-time PCR and western blot respectively. Cell counting Kit-8, clone formation assay, Transwell assay were used to determine the effect of P4HA3 on the proliferative, invasive and migratory capacities of head and neck squamous cell carcinoma cells.

RESULTS

Bioinformatics analysis showed that P4HA3 was up-regulated in head and neck squamous cell carcinoma tissues, and had an independent prognostic value for head and neck squamous cell carcinoma patients. The outcomes of gain- and loss-of-function tests illustrated that P4HA3 significantly boosted head and neck squamous cell carcinoma cell proliferative, invasive and migratory abilities. Besides, western blot assay demonstrated that P4HA3 could remarkably activate the epithelial-mesenchymal transition process, with reduced the level of E-cadherin and up-regulated the levels of N-cadherin, Vimentin and Snail.

CONCLUSION

We deduce that P4HA3 acts as an oncogene that raises tumor cell viability and metastasis partly by inducing the epithelial-mesenchymal transition process, suggesting that P4HA3 may be considered as a valuable biomarker for head and neck squamous cell carcinoma treatment.

摘要

目的

本研究旨在探讨脯氨酰 4-羟化酶亚基 α3(P4HA3)在头颈部鳞状细胞癌中的预后价值和功能作用。

方法

我们下载了头颈部鳞状细胞癌的 RNA-Seq 数据集,用于分析 P4HA3 的表达情况并确定其预后价值。选择头颈部鳞状细胞癌细胞系 CAL27 和 FaDu 进行 P4HA3 的功能获得和功能丧失试验。通过实时定量 PCR 和 Western blot 分别检测头颈部鳞状细胞癌细胞中 P4HA3 的 mRNA 和蛋白水平。细胞计数试剂盒-8、克隆形成实验和 Transwell 实验用于确定 P4HA3 对头颈部鳞状细胞癌细胞增殖、侵袭和迁移能力的影响。

结果

生物信息学分析显示,P4HA3 在头颈部鳞状细胞癌组织中上调,对头颈部鳞状细胞癌患者具有独立的预后价值。功能获得和功能丧失试验的结果表明,P4HA3 显著促进头颈部鳞状细胞癌细胞的增殖、侵袭和迁移能力。此外,Western blot 实验表明,P4HA3 可以显著激活上皮-间充质转化过程,降低 E-钙黏蛋白水平,上调 N-钙黏蛋白、波形蛋白和 Snail 的水平。

结论

我们推断 P4HA3 作为一种癌基因,通过诱导上皮-间充质转化过程,提高肿瘤细胞的活力和转移能力,这表明 P4HA3 可能被认为对头颈部鳞状细胞癌治疗有价值的生物标志物。

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