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基于机器学习鉴定潜在的长链非编码RNA和微小RNA作为甲状腺乳头状癌的诊断生物标志物

Identification of Potential lncRNAs and miRNAs as Diagnostic Biomarkers for Papillary Thyroid Carcinoma Based on Machine Learning.

作者信息

Yang Fei, Zhang Jie, Li Baokun, Zhao Zhijun, Liu Yan, Zhao Zhen, Jing Shanghua, Wang Guiying

机构信息

Department of Otolaryngology-Head and Neck Surgery, The Fourth Hospital of Hebei Medical University, Hebei, China.

General Surgical Department, The Fourth Hospital of Hebei Medical University, Hebei, China.

出版信息

Int J Endocrinol. 2021 Jul 21;2021:3984463. doi: 10.1155/2021/3984463. eCollection 2021.

DOI:10.1155/2021/3984463
PMID:34335744
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8318749/
Abstract

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.

摘要

背景

甲状腺乳头状癌（PTC）在甲状腺癌（TC）中占比最大。本研究的目的是鉴定诊断性、差异表达的长链非编码RNA（lncRNA）和微小RNA（miRNA），以有助于理解PTC的表观遗传机制。

方法

从癌症基因组图谱（TCGA）数据集中下载lncRNA、miRNA和mRNA数据，随后对差异表达的mRNA进行功能分析。通过随机森林鉴定最佳诊断lncRNA和miRNA生物标志物。鉴定最佳诊断lncRNA与mRNA以及最佳诊断miRNA与mRNA之间的调控网络，随后构建lncRNA - mRNA - miRNA的竞争性内源RNA（ceRNA）网络。对lncRNA、miRNA和mRNA进行表达验证和诊断分析。在PTC - UC3细胞系中过表达ADD3 - AS1，并使用细胞增殖和侵袭试验研究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被视为PTC的最佳诊断生物标志物。鉴定出通过上述诊断性lncRNA和miRNA的表观遗传修饰，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分别参与细胞黏附和内皮细胞迁移。ADD3 - AS1的过表达抑制了PTC细胞系中的细胞生长和侵袭。

结论

所鉴定的lncRNA/miRNA/mRNA在正常组织和癌组织之间存在差异表达。此外，鉴定出的lncRNA和miRNA改变可能是PTC的潜在诊断生物标志物。此外，通过上述lncRNA和miRNA的表观遗传修饰可能参与PTC的肿瘤发生。

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