Otorhinolaryngology Hospital, The First Affiliated Hospital, Sun Yat-sen University , Guangzhou, Guangdong, China.
Department of Otolaryngology, The Eighth Affiliated Hospital, Sun Yat-sen University , Shenzhen, Guangdong, P.R. China.
RNA Biol. 2020 Jul;17(7):977-989. doi: 10.1080/15476286.2020.1741282. Epub 2020 Mar 30.
Accumulating evidence indicates that lncRNAs can interact with miRNAs to regulate target mRNAs through competitive interactions. However, this mechanism remains largely unexplored in laryngeal squamous cell carcinoma (LSCC). In this study, transcriptome-wide RNA sequencing was performed on 3 pairs of LSCC tissues and adjacent normal tissues to investigate the expression profiles of lncRNAs, miRNAs and mRNAs, with differential expression of 171 lncRNAs, 36 miRNAs and 1709 mRNAs detected. Seven lncRNAs, eight mRNAs and three miRNAs were identified to be dysregulated in patients' tissues by using qRT-PCR. GO and KEGG pathway enrichment analyses were performed to elucidate the potential functions of these differentially expressed genes in LSCC. Subsequently, a ceRNA (lncRNA-miRNA-mRNA) network including 4631 ceRNA pairs was constructed based on predicted miRNAs shared by lncRNAs and mRNAs. Cis- and transregulatory lncRNAs were analysed by bioinformatics-based methods. Importantly, mRNA-related ceRNA networks (mRCNs) were further obtained based on potential cancer-related coding genes. Coexpression between lncRNAs and downstream mRNAs was used as a criterion for the validation of mRCNs, with the ZNF561-AS1-miR217-WNT5A and SATB1-AS1-miR1299-SAV1/CCNG2/SH3 KBP1/JADE1/HIPK2 ceRNA regulatory interactions determined, followed by experimental validation after siRNA transfection. Moreover, ceRNA activity analysis revealed that different activities of ceRNA modules existing in specific pathological environments may contribute to the tumorigenesis of LSCC. Consistently, both downregulated SATB1-AS1 and ZNF561-AS1 significantly promoted laryngeal cancer cell migration and invasion, indicating their important roles in LSCC via a ceRNA regulatory mechanism. Taken together, the results of this investigation uncovered and systemically characterized a lncRNA-related ceRNA regulatory network that may be valuable for the diagnosis and treatment of LSCC.
越来越多的证据表明，lncRNAs 可以与 miRNAs 相互作用，通过竞争性相互作用来调节靶 mRNAs。然而，这种机制在喉鳞状细胞癌 (LSCC) 中仍在很大程度上未被探索。在这项研究中，对 3 对 LSCC 组织和相邻正常组织进行了全转录组 RNA 测序，以研究 lncRNAs、miRNAs 和 mRNAs 的表达谱，通过 qRT-PCR 检测到 171 个 lncRNAs、36 个 miRNAs 和 1709 个 mRNAs 的差异表达。通过 qRT-PCR 鉴定出 7 个 lncRNA、8 个 mRNA 和 3 个 miRNA 在患者组织中失调。进行 GO 和 KEGG 通路富集分析以阐明这些差异表达基因在 LSCC 中的潜在功能。随后，基于预测的 lncRNA 和 mRNA 之间共享的 miRNA，构建了包含 4631 个 ceRNA 对的 ceRNA (lncRNA-miRNA-mRNA) 网络。通过基于生物信息学的方法分析顺式和反式调节 lncRNAs。重要的是，基于潜在的癌症相关编码基因进一步获得了 mRNA 相关的 ceRNA 网络 (mRCN)。lncRNA 和下游 mRNAs 之间的共表达被用作验证 mRCN 的标准，确定了 ZNF561-AS1-miR217-WNT5A 和 SATB1-AS1-miR1299-SAV1/CCNG2/SH3 KBP1/JADE1/HIPK2 ceRNA 调节相互作用，随后通过 siRNA 转染进行了实验验证。此外，ceRNA 活性分析表明，在特定病理环境中存在的 ceRNA 模块的不同活性可能有助于 LSCC 的肿瘤发生。一致地，下调的 SATB1-AS1 和 ZNF561-AS1 均显著促进喉癌细胞迁移和侵袭，表明它们通过 ceRNA 调节机制在 LSCC 中具有重要作用。总之，这项研究的结果揭示并系统地描述了一个可能对 LSCC 的诊断和治疗有价值的 lncRNA 相关 ceRNA 调节网络。
