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晚期喉鳞状细胞癌中长链非编码RNA和mRNA表达谱的综合分析

Integrated Analysis of Long Noncoding RNA and mRNA Expression Profile in Advanced Laryngeal Squamous Cell Carcinoma.

作者信息

Feng Ling, Wang Ru, Lian Meng, Ma Hongzhi, He Ning, Liu Honggang, Wang Haizhou, Fang Jugao

机构信息

Department of Otorhinolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, China.

Key Laboratory of Otorhinolaryngology Head and Neck Surgery, Ministry of Education, Beijing, China.

出版信息

PLoS One. 2016 Dec 29;11(12):e0169232. doi: 10.1371/journal.pone.0169232. eCollection 2016.

Abstract

Long non-coding RNA (lncRNA) plays an important role in tumorigenesis. However, the expression pattern and function of lncRNAs in laryngeal squamous cell carcinoma (LSCC) are still unclear. To investigate the aberrantly expressed lncRNAs and mRNAs in advanced LSCC, we screened lncRNA and mRNA expression profiles in 9 pairs of primary Stage IVA LSCC tissues and adjacent non-neoplastic tissues by lncRNA and mRNA integrated microarrays. Gene Ontology and pathway analysis were performed to find out the significant function and pathway of the differentially expressed mRNAs, gene-gene functional interaction network and ceRNA network were constructed to select core mRNAs, and lncRNA-mRNA expression correlation network was built to identify the interactions between lncRNA and mRNA. qRT-PCR was performed to further validate the expressions of selected lncRNAs and mRNAs in advanced LSCC. We found 1459 differentially expressed lncRNAs and 2381 differentially expressed mRNAs, including 846 up-regulated lncRNAs and 613 down-regulated lncRNAs, 1542 up-regulated mRNAs and 839 down-regulated mRNAs. The mRNAs ITGB1, HIF1A, and DDIT4 were selected as core mRNAs, which are mainly involved in biological processes, such as matrix organization, cell cycle, adhesion, and metabolic pathway. LncRNA-mRNA expression correlation network showed LncRNA NR_027340, MIR31HG were positively correlated with ITGB1, HIF1A respectively. LncRNA SOX2-OT was negatively correlated with DDIT4. qRT-PCR further validated the expression of these lncRNAs and mRNAs. The work provides convincing evidence that the identified lncRNAs and mRNAs are potential biomarkers in advanced LSCC for further future studies.

摘要

长链非编码RNA(lncRNA)在肿瘤发生过程中发挥着重要作用。然而,lncRNAs在喉鳞状细胞癌(LSCC)中的表达模式和功能仍不清楚。为了研究晚期LSCC中异常表达的lncRNAs和mRNAs,我们通过lncRNA和mRNA整合微阵列筛选了9对原发性IVA期LSCC组织及相邻非肿瘤组织中的lncRNA和mRNA表达谱。进行基因本体论和通路分析以找出差异表达mRNA的显著功能和通路,构建基因-基因功能相互作用网络和ceRNA网络以选择核心mRNA,并构建lncRNA-mRNA表达相关网络以识别lncRNA与mRNA之间的相互作用。进行qRT-PCR以进一步验证晚期LSCC中所选lncRNAs和mRNAs的表达。我们发现1459个差异表达的lncRNAs和2381个差异表达的mRNAs,其中包括846个上调的lncRNAs和613个下调的lncRNAs,1542个上调的mRNAs和839个下调的mRNAs。选择mRNA ITGB1、HIF1A和DDIT4作为核心mRNA,它们主要参与生物学过程,如基质组织、细胞周期、黏附及代谢途径。lncRNA-mRNA表达相关网络显示LncRNA NR_027340、MIR31HG分别与ITGB1、HIF1A呈正相关。LncRNA SOX2-OT与DDIT4呈负相关。qRT-PCR进一步验证了这些lncRNAs和mRNAs的表达。该研究提供了令人信服的证据,表明所鉴定的lncRNAs和mRNAs是晚期LSCC中潜在的生物标志物,可供未来进一步研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/152f/5199101/75ac0c87fb03/pone.0169232.g001.jpg

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