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与口腔黏膜下纤维化恶性进展相关的长链非编码RNA表达谱

Long Non-Coding RNA Expression Profile Associated with Malignant Progression of Oral Submucous Fibrosis.

作者信息

Zhou Shanghui, Zhu Yun, He Zhijing, Zhang Dahe, Guo Feng, Jian Xinchun, Zhang Chenping

机构信息

Department of Oral & Maxillofacial - Head & Neck Oncology, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China.

National Clinical Research Center for Oral Diseases, China.

出版信息

J Oncol. 2019 Jul 29;2019:6835176. doi: 10.1155/2019/6835176. eCollection 2019.

Abstract

Oral submucous fibrosis (OSF) as one of the premalignant disorders endures a series of histopathological stages to invasive oral squamous cell carcinoma (OSCC) eventually. However, the role of long non-coding RNA (lncRNA) expression in OSF malignant progression still remains poorly understood. Through RNA-sequencing normal mucous, OSF and OSCC tissues, we found 687 lncRNA transcripts significantly and differentially expressed during OSF progression, including 231 upregulated lncRNAs and 456 downregulated lncRNAs, indicating that lncRNAs are involved in the regulation of different stages of OSF development. Further functional enrichment analysis showed these differentially expressed lncRNAs participated in inflammation signaling, Wnt signaling, angiogenesis, CCKR signaling, integrin signaling, PDGF signaling, p53 signaling, and EGF receptor (EGFR) signaling pathways, which contribute to inflammatory and fibroelastic pathogenetic changes of OSF and further malignant progression. Five novel lncRNAs were differentially expressed during OSF progression with varied expression levels, indicating the importance of these lncRNAs in OSF malignant development. Moreover, some lncRNAs have been previously identified to be associated with OSCC pathogenesis, including and . Thus, our study firstly comprehensively elucidated lncRNAs expression profile of malignant procession from OSF premalignant lesion to OSCC, which will enlighten our understanding of the importance of lncRNA involved in OSF malignant development.

摘要

口腔黏膜下纤维化(OSF)作为一种癌前病变,最终会经历一系列组织病理学阶段发展为侵袭性口腔鳞状细胞癌(OSCC)。然而,长链非编码RNA(lncRNA)表达在OSF恶性进展中的作用仍知之甚少。通过对正常黏膜、OSF和OSCC组织进行RNA测序,我们发现在OSF进展过程中有687个lncRNA转录本显著差异表达,其中包括231个上调的lncRNA和456个下调的lncRNA,这表明lncRNA参与了OSF发展不同阶段的调控。进一步的功能富集分析表明,这些差异表达的lncRNA参与了炎症信号、Wnt信号、血管生成、CCKR信号、整合素信号、血小板衍生生长因子(PDGF)信号、p53信号和表皮生长因子受体(EGFR)信号通路,这些通路导致了OSF的炎症和纤维弹性致病变化以及进一步的恶性进展。在OSF进展过程中,有5种新的lncRNA差异表达且表达水平各异,这表明这些lncRNA在OSF恶性发展中具有重要意义。此外,先前已确定一些lncRNA与OSCC发病机制相关,包括 和 。因此,我们的研究首次全面阐明了从OSF癌前病变到OSCC恶性进程中的lncRNA表达谱,这将有助于我们理解lncRNA在OSF恶性发展中的重要性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d26/6699286/60c15e8c2bc7/JO2019-6835176.001.jpg

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