Xia Fada, Wang Wenlong, Jiang Bo, Chen Yong, Li Xinying
Department of General Surgery, Xiangya Hospital, Central South University, Changsha 410008, People's Republic of China,
Cancer Manag Res. 2019 Feb 8;11:1249-1262. doi: 10.2147/CMAR.S184566. eCollection 2019.
Papillary thyroid carcinoma (PTC) is the most common endocrine malignancy and its incidence has increased over the last few decades. The molecular mechanisms underlying PTC tumorigenesis and progression are still unclear.
The microRNA (miRNA) expression patterns of PTC were revealed by miRNA microarray analysis and validated with The Cancer Genome Atlas (TCGA) data. Promoter DNA methylation rates of miR-204 were analyzed by Agena Methylation MassAR-RAY analysis and validated with TCGA data. The underlying molecular mechanisms of miR-204 involved in PTC were studied by bioinformatics analyses.
A total of 181 differentially expressed miRNAs (89 downregulated and 92 upregulated miRNAs) between PTC and normal tissues were detected in this study. We identified miR-204 as one of the most significantly downregulated miRNAs in PTC. Downregulation of miR-204 was related to PTC extrathyroidal extension, high T-stage, lymph metastasis, BRAF V600E mutation, and aggressive tall cell variant. The Agena MassARRAY results indicated that 12 CpG sites located at the promoter of miR-204 were hypermethylated in PTC tissues compared to normal tissues. The promoter methylation rates of miR-204 in PTC were negatively correlated with the expression levels of miR-204 and its host gene Downregulated miR-204 expression was related to several important pathways and mechanisms involved in tumorigenesis and progression.
Promoter DNA methylation-silenced miR-204 could serve as a potential diagnostic biomarker of PTC. Downregulation of miR-204 may play an important role in PTC via its involvement in many tumor-related pathways. Novel target genes and putative mechanisms of miR-204 in PTC need to be further validated.
甲状腺乳头状癌（PTC）是最常见的内分泌恶性肿瘤，在过去几十年中其发病率有所上升。PTC发生和进展的分子机制仍不清楚。
通过miRNA微阵列分析揭示PTC的微小RNA（miRNA）表达模式，并用癌症基因组图谱（TCGA）数据进行验证。通过Agena甲基化质谱分析检测miR-204的启动子DNA甲基化率，并用TCGA数据进行验证。通过生物信息学分析研究miR-204参与PTC的潜在分子机制。
本研究共检测到PTC与正常组织之间181个差异表达的miRNA（89个下调和92个上调的miRNA）。我们将miR-204鉴定为PTC中下调最显著的miRNA之一。miR-204的下调与PTC甲状腺外侵犯、高T分期、淋巴转移、BRAF V600E突变以及侵袭性高细胞变体有关。Agena MassARRAY结果表明，与正常组织相比，PTC组织中位于miR-204启动子的12个CpG位点发生了高甲基化。PTC中miR-204的启动子甲基化率与miR-204及其宿主基因的表达水平呈负相关。miR-204表达下调与肿瘤发生和进展中涉及的几个重要途径和机制有关。
启动子DNA甲基化沉默的miR-204可作为PTC的潜在诊断生物标志物。miR-204的下调可能通过参与许多肿瘤相关途径在PTC中发挥重要作用。miR-204在PTC中的新靶基因和推定机制需要进一步验证。
