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喉鳞状细胞癌全编码和非编码RNA转录组表达谱的综合分析及环状RNA-长链非编码RNA共调控的竞争性内源RNA网络构建

Comprehensive analysis of the whole coding and non-coding RNA transcriptome expression profiles and construction of the circRNA-lncRNA co-regulated ceRNA network in laryngeal squamous cell carcinoma.

作者信息

Zhao Rui, Li Feng-Qing, Tian Lin-Li, Shang De-Si, Guo Yan, Zhang Jia-Rui, Liu Ming

机构信息

Department of Otolaryngology-Head and Neck Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150081, Heilongjiang, China.

Department of Gerontology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.

出版信息

Funct Integr Genomics. 2019 Jan;19(1):109-121. doi: 10.1007/s10142-018-0631-y. Epub 2018 Aug 21.

DOI:10.1007/s10142-018-0631-y
PMID:30128795
Abstract

Recently, accumulating evidence has demonstrated that non-coding RNAs (ncRNAs) play a vital role in oncogenicity. Nevertheless, the regulatory mechanisms and functions remain poorly understood, especially for lncRNAs and circRNAs. In this study, we simultaneously detected, for the first time, the expression profiles of the whole transcriptome, including miRNA, circRNA and lncRNA + mRNA, in five pairs of laryngeal squamous cell carcinoma (LSCC) and matched non-carcinoma tissues by microarrays. Five miRNAs, four circRNAs, three lncRNAs and five mRNAs that were dysregulated were selected to confirm the verification of the microarray data by quantitative real-time PCR (qRT-PCR) in 20 pairs of LSCC samples. We constructed LSCC-related competing endogenous RNA (ceRNA) networks of lncRNAs and circRNAs (circRNA or lncRNA-miRNA-mRNA) respectively. Functional annotation revealed the lncRNA-mediated ceRNA network were enriched for genes involved in the tumor-associated pathways. Hsa_circ_0033988 with the highest degree in the circRNA-mediated ceRNA network was associated with fatty acid degradation, which was responsible for the depletion of fat in tumor-associated cachexia. Finally, to clarify the ncRNA co-regulation mechanism, we constructed a circRNA-lncRNA co-regulated network by integrating the above two networks and identified 9 modules for further study. A subnetwork of module 2 with the most dysregulated microRNAs was extracted to establish the ncRNA-involved TGF-β-associated pathway. In conclusion, our findings provide a high-throughput microarray data of the coding and non-coding RNAs and establish the foundation for further functional research on the ceRNA regulatory mechanism of non-coding RNAs in LSCC.

摘要

最近,越来越多的证据表明非编码RNA(ncRNAs)在致癌性中起着至关重要的作用。然而,其调控机制和功能仍知之甚少,尤其是长链非编码RNA(lncRNAs)和环状RNA(circRNAs)。在本研究中,我们首次通过微阵列同时检测了五对喉鳞状细胞癌(LSCC)及其匹配的非癌组织中整个转录组的表达谱,包括miRNA、circRNA以及lncRNA + mRNA。选择五个失调的miRNA、四个circRNA、三个lncRNA和五个mRNA,通过定量实时PCR(qRT-PCR)在20对LSCC样本中对微阵列数据进行验证。我们分别构建了lncRNAs和circRNAs(circRNA或lncRNA-miRNA-mRNA)相关的LSCC竞争性内源RNA(ceRNA)网络。功能注释显示lncRNA介导的ceRNA网络富含参与肿瘤相关途径的基因。circRNA介导的ceRNA网络中度数最高的hsa_circ_0033988与脂肪酸降解有关,脂肪酸降解是肿瘤相关恶病质中脂肪消耗的原因。最后为阐明ncRNA的共同调控机制,我们通过整合上述两个网络构建了一个circRNA-lncRNA共同调控网络,并确定了9个模块以供进一步研究。提取模块2中失调miRNA最多的一个子网,以建立涉及ncRNA的TGF-β相关途径。总之,我们的研究结果提供了编码和非编码RNA的高通量微阵列数据,并为进一步研究LSCC中ncRNA的ceRNA调控机制的功能奠定了基础。

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