多能性转录因子Nanog及其与口腔鳞状细胞癌整体进展、顺铂耐药、侵袭和干性获得的关系。

Pluripotency transcription factor Nanog and its association with overall oral squamous cell carcinoma progression, cisplatin-resistance, invasion and stemness acquisition.

作者信息

Kashyap Tanushree, Nath Nidhi, Mishra Prajna, Jha Arpita, Nagini Siddavaram, Mishra Rajakishore

机构信息

Department of Life Sciences, School of Natural Sciences, Central University of Jharkhand, Ranchi, Jharkhand, India.

Centre for Applied Chemistry, School of Natural Sciences, Central University of Jharkhand, Ranchi, Jharkhand, India.

出版信息

Head Neck. 2020 Nov;42(11):3282-3294. doi: 10.1002/hed.26373. Epub 2020 Jul 25.

DOI:10.1002/hed.26373

PMID:32710593

Abstract

BACKGROUND

Cisplatin-resistant oral squamous cell carcinoma (OSCC) cells acquire stem-like characteristics and are difficult to treat. Nanog is a transcription factor and needed for maintenance of pluripotency, but its transcription-promoting role in OSCC progression and cisplatin resistance is poorly understood.

METHODS

Here, 110 fresh human tissue specimens of various stages, including invasive (N )/chemoradiation-resistant OSCC samples, cisplatin-resistant (CisR-SCC-4/-9) OSCC cells/parental cells, photochemical ECGC, and siRNA (Nanog) were used.

RESULTS

Nanog overexpression was associated with overall progression, chemoresistance, and invasion of OSCC. Nanog recruitment to c-Myc, Slug, E-cadherin, and Oct-4 gene promoter was observed. Positive correlation of Nanog protein expression with c-Myc, Slug, cyclin D1, MMP-2/-9, and Oct-4 and negative correlation with E-cadherin gene expression were found. Knockdown of Nanog and treatment of epicatechin-3-gallate reversed cisplatin resistance and diminished invasion/migration potential.

CONCLUSION

Nanog directly participated in the regulation of Slug, E-cadherin, Oct-4, and c-Myc genes, causing cisplatin resistance/recurrence of OSCC.

摘要

背景

顺铂耐药的口腔鳞状细胞癌（OSCC）细胞具有干细胞样特征，难以治疗。Nanog是一种转录因子，对维持多能性至关重要，但其在OSCC进展和顺铂耐药中的转录促进作用尚不清楚。

方法

本研究使用了110份不同阶段的新鲜人体组织标本，包括侵袭性（N）/放化疗耐药的OSCC样本、顺铂耐药（CisR-SCC-4/-9）的OSCC细胞/亲本细胞、光化学表没食子儿茶素没食子酸酯（ECGC）以及小干扰RNA（siRNA，针对Nanog）。

结果

Nanog过表达与OSCC的总体进展、化疗耐药和侵袭相关。观察到Nanog募集至c-Myc、Slug、E-钙黏蛋白和Oct-4基因启动子区域。发现Nanog蛋白表达与c-Myc、Slug、细胞周期蛋白D1、基质金属蛋白酶-2/-9以及Oct-4呈正相关，与E-钙黏蛋白基因表达呈负相关。敲低Nanog以及表没食子儿茶素-3-没食子酸酯处理可逆转顺铂耐药并降低侵袭/迁移潜能。