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微小RNA和长链非编码RNA作为口腔鳞状细胞癌发生发展过程中NANOG表达的调节因子

MicroRNAs and Long Non-Coding RNAs as Regulators of NANOG Expression in the Development of Oral Squamous Cell Carcinoma.

作者信息

Grubelnik Gašper, Boštjančič Emanuela, Aničin Aleksandar, Dovšak Tadej, Zidar Nina

机构信息

Institute of Pathology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.

Department of Otorhinolaryngology and Cervicofacial Surgery, University Medical Centre Ljubljana, Ljubljana, Slovenia.

出版信息

Front Oncol. 2021 Feb 11;10:579053. doi: 10.3389/fonc.2020.579053. eCollection 2020.

DOI:10.3389/fonc.2020.579053
PMID:33643897
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7906007/
Abstract

NANOG is a stem cell transcription factor that is believed to play an important role in the development of oral squamous cell carcinoma (OSCC), but there is limited data regarding the role of long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) in the regulation of NANOG expression. We therefore analyzed expression of NANOG, NANOG-regulating miRNAs and lncRNAs in OSCC cancerogenesis, using oral biopsy samples from 66 patients including normal mucosa, dysplasia, and OSCC. Expression analysis of , , , , , , and was performed using qPCR and immunohistochemistry for NANOG protein detection. NANOG protein showed no staining in normal mucosa, very weak in low-grade dysplasia, and strong staining in high-grade dysplasia and OSCC. , , , and showed up-regulation, and showed down-regulation, and showed variable expression during cancerogenesis. NANOG mRNA was up-regulated early in cancerogenesis, before strong protein expression can be detected. was in correlation with and . Our results suggest that miRNAs and lncRNAs, particularly and , might be important post-transcription regulatory mechanisms of NANOG in OSCC cancerogenesis. Furthermore, NANOG protein detection has a diagnostic potential for oral high-grade dysplasia, distinguishing it from low-grade dysplasia and non-neoplastic reactive lesions.

摘要

NANOG是一种干细胞转录因子，被认为在口腔鳞状细胞癌（OSCC）的发生发展中起重要作用，但关于长链非编码RNA（lncRNA）和微小RNA（miRNA）在NANOG表达调控中的作用的数据有限。因此，我们使用66例患者的口腔活检样本（包括正常黏膜、发育异常和OSCC）分析了NANOG、调控NANOG的miRNA和lncRNA在OSCC发生过程中的表达情况。使用qPCR和免疫组织化学对NANOG蛋白进行检测，对[此处原文缺失具体基因名称]、[此处原文缺失具体基因名称]、[此处原文缺失具体基因名称]、[此处原文缺失具体基因名称]、[此处原文缺失具体基因名称]、[此处原文缺失具体基因名称]和[此处原文缺失具体基因名称]进行表达分析。NANOG蛋白在正常黏膜中无染色，在低度发育异常中染色非常弱，在高度发育异常和OSCC中染色强。[此处原文缺失具体基因名称]、[此处原文缺失具体基因名称]、[此处原文缺失具体基因名称]和[此处原文缺失具体基因名称]呈上调，[此处原文缺失具体基因名称]和[此处原文缺失具体基因名称]呈下调，[此处原文缺失具体基因名称]在肿瘤发生过程中表达可变。在可检测到强烈的蛋白表达之前，NANOG mRNA在肿瘤发生早期就上调。[此处原文缺失具体基因名称]与[此处原文缺失具体基因名称]和[此处原文缺失具体基因名称]相关。我们的结果表明，miRNA和lncRNA，特别是[此处原文缺失具体基因名称]和[此处原文缺失具体基因名称]，可能是OSCC发生过程中NANOG重要的转录后调控机制。此外，NANOG蛋白检测对口腔高度发育异常具有诊断潜力，可将其与低度发育异常和非肿瘤性反应性病变区分开来。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6c5/7906007/8b04f195baef/fonc-10-579053-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6c5/7906007/79364cf5bef2/fonc-10-579053-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6c5/7906007/b41159185eaf/fonc-10-579053-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6c5/7906007/c608a2d4f600/fonc-10-579053-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6c5/7906007/c2ac9930b19a/fonc-10-579053-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6c5/7906007/8b04f195baef/fonc-10-579053-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6c5/7906007/79364cf5bef2/fonc-10-579053-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6c5/7906007/b41159185eaf/fonc-10-579053-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6c5/7906007/c608a2d4f600/fonc-10-579053-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6c5/7906007/c2ac9930b19a/fonc-10-579053-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6c5/7906007/8b04f195baef/fonc-10-579053-g005.jpg

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