Department of Surgery, The Sixth People's Hospital Affiliated to Shanghai Jiao Tong University, Shanghai 200233, P.R. China.
Mol Med Rep. 2013 Nov;8(5):1353-8. doi: 10.3892/mmr.2013.1699. Epub 2013 Sep 24.
microRNAs (miRNAs) are involved in the pathogenesis of diverse human cancers through its target genes, including papillary thyroid cancer (PTC). However, there are few studies regarding associations between clinicopathological features of PTC with the expression of specific miRNAs and its potential target genes. In the present study, analysis of miRNA was integrated with mRNA expression profiles in aggressive PTC. miRNA and gene expression arrays were used to identify a subset of differentially expressed miRNAs and mRNAs between aggressive and non-aggressive PTCs. These miRNAs and mRNAs were further validated by qPCR in a cohort of 20 PTCs with extrathyroidal invasion and/or distant metastases, and 20 PTCs with no extrathyroidal invasion. The target of these miRNAs was determined by luciferase reporter and bioinformatic analysis. The miRNA arrays identified 14 upregulated miRNAs and 10 downregulated miRNAs in aggressive compared with non-aggressive PTCs. Significant miRNA deregulation was confirmed in the validation cohort, with upregulation of miR-146b-5p and miR-221/222 and downregulation of miR-16 and miR-613 in aggressive PTCs. The gene arrays identified 2000 differentially expressed genes, in which TIMP3, ZNFR3, FN1 and ITGA2 were observed to be target genes inversely correlated with miR-221/222, miR-146b-5p, miR-613 and miR-16, respectively. The results of the present study indicated the potential importance of miR-221/222, miR-146b-5p, miR-16 and miR-613 in determining the aggressive properties of PTC by targeting TIMP3, ZNFR3, FN1 and ITGA2, respectively. Additional studies should be conducted to confirm the results.
微小 RNA（miRNAs）通过其靶基因参与多种人类癌症的发病机制，包括甲状腺乳头状癌（PTC）。然而，关于 PTC 的临床病理特征与特定 miRNAs 及其潜在靶基因表达之间的关联的研究较少。在本研究中，miRNA 分析与侵袭性 PTC 的 mRNA 表达谱相结合。使用 miRNA 和基因表达阵列来鉴定侵袭性和非侵袭性 PTC 之间差异表达的 miRNA 和 mRNAs 子集。这些 miRNA 和 mRNAs 在 20 例有甲状腺外侵犯和/或远处转移和 20 例无甲状腺外侵犯的 PTC 患者的队列中通过 qPCR 进一步验证。这些 miRNA 的靶基因通过荧光素酶报告和生物信息学分析确定。miRNA 阵列鉴定出 14 个上调的 miRNA 和 10 个下调的 miRNA 在侵袭性 PTC 中与非侵袭性 PTC 相比。在验证队列中证实了显著的 miRNA 失调，侵袭性 PTC 中 miR-146b-5p 和 miR-221/222 上调，miR-16 和 miR-613 下调。基因阵列鉴定出 2000 个差异表达的基因，其中 TIMP3、ZNFR3、FN1 和 ITGA2 被观察为与 miR-221/222、miR-146b-5p、miR-613 和 miR-16 分别呈负相关的靶基因。本研究的结果表明，miR-221/222、miR-146b-5p、miR-16 和 miR-613 通过靶向 TIMP3、ZNFR3、FN1 和 ITGA2，分别在决定 PTC 的侵袭性方面具有重要意义。应进行更多的研究来证实这些结果。
