Background. Papillary thyroid carcinoma (PTC) accounts for most of the proportion of thyroid cancer (TC). The objective of this study was to identify diagnostic, differentially expressed long noncoding RNAs (lncRNAs) and microRNAs (miRNAs), contributing to understanding the epigenetics mechanism of PTC. Methods. The data of lncRNA, miRNA, and mRNA were downloaded from the Cancer Genome Atlas (TCGA) dataset, followed by functional analysis of differentially expressed mRNAs. Optimal diagnostic lncRNA and miRNA biomarkers were identified via random forest. The regulatory network between optimal diagnostic lncRNA and mRNAs and optimal diagnostic miRNA and mRNAs was identified, followed by the construction of ceRNA network of lncRNA-mRNA-miRNA. Expression validation and diagnostic analysis of lncRNAs, miRNAs, and mRNAs were performed. Overexpression of ADD3-AS1 was performed in PTC-UC3 cell lines, and cell proliferation and invasion assay were used for investigating the role of ADD3-AS1 in PTC. Results. A total of 107 differentially expressed lncRNAs, 81 differentially expressed miRNAs, and 515 differentially expressed mRNAs were identified. 11 lncRNAs and 6 miRNAs were regarded as the optimal diagnostic biomarkers for PTC. The epigenetic modifications via the above diagnostic lncRNAs and miRNAs were identified, including MIR181A2HG-FOXP2-hsa-miR-146b-3p, BLACAT1/ST7-AS1-RPS6KA5-hsa-miR-34a-5p, LBX2-AS1/MIR100HG-CDHR3-hsa-miR-34a-5p, ADD3-AS1-PTPRE-hsa-miR-9-5p, ADD3-AS1-TGFBR1-hsa-miR-214-3p, LINC00506-MMRN1-hsa-miR-4709-3p, and LOC339059-STK32A-hsa-miR-199b-5p. In the functional analysis, MMRN1 and TGFBR1 were involved in cell adhesion and endothelial cell migration, respectively. Overexpression of ADD3-AS1 inhibited cell growth and invasion in PTC cell lines. Conclusion. The identified lncRNAs/miRNAs/mRNA were differentially expressed between normal and cancerous tissues. In addition, identified altered lncRNAs and miRNAs may be potential diagnostic biomarkers for PTC. Additionally, epigenetic modifications via the above lncRNAs and miRNAs may be involved in tumorigenesis of PTC.

中文翻译：

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基于机器学习识别潜在的 lncRNA 和 miRNA 作为甲状腺乳头状癌的诊断生物标志物

背景。甲状腺乳头状癌（PTC）占甲状腺癌（TC）的大部分。本研究的目的是鉴定诊断性、差异表达的长链非编码 RNA (lncRNA) 和 microRNA (miRNA)，有助于了解 PTC 的表观遗传学机制。方法. 从癌症基因组图谱（TCGA）数据集中下载lncRNA、miRNA和mRNA的数据，然后对差异表达的mRNA进行功能分析。通过随机森林确定最佳诊断 lncRNA 和 miRNA 生物标志物。确定了最优诊断lncRNA和mRNA与最优诊断miRNA和mRNA之间的调控网络，构建了lncRNA-mRNA-miRNA的ceRNA网络。进行了 lncRNA、miRNA 和 mRNA 的表达验证和诊断分析。ADD3-AS1过表达在PTC-UC3细胞系中进行，细胞增殖和侵袭试验用于研究ADD3-AS1在PTC中的作用。结果. 共鉴定出107个差异表达的lncRNA、81个差异表达的miRNA和515个差异表达的mRNA。11 个 lncRNA 和 6 个 miRNA 被认为是 PTC 的最佳诊断生物标志物。通过上述诊断性 lncRNA 和 miRNA 进行的表观遗传修饰被鉴定，包括 MIR181A2HG-FOXP2-hsa-miR-146b-3p、BLACAT1/ST7-AS1-RPS6KA5-hsa-miR-34a-5p、LBX2-AS1/MIR100HG-CDHR3- hsa-miR-34a-5p、ADD3-AS1-PTPRE-hsa-miR-9-5p、ADD3-AS1-TGFBR1-hsa-miR-214-3p、LINC00506-MMRN1-hsa-miR-4709-3p 和 LOC339059 -STK32A-hsa-miR-199b-5p。在功能分析中，MMRN1和TGFBR1分别参与细胞粘附和内皮细胞迁移。ADD3-AS1 的过表达抑制了 PTC 细胞系中的细胞生长和侵袭。结论. 鉴定出的 lncRNAs/miRNAs/mRNA 在正常组织和癌组织之间存在差异表达。此外，鉴定出的改变的 lncRNA 和 miRNA 可能是 PTC 的潜在诊断生物标志物。此外，通过上述 lncRNA 和 miRNA 进行的表观遗传修饰可能参与 PTC 的肿瘤发生。