甲状腺乳头癌中 microRNA 的失调及其与 BRAF V600E 突变的关系。
MicroRNA Deregulation in Papillary Thyroid Cancer and its Relationship With BRAF V600E Mutation.
机构信息
Department of Otorhinolaryngology and Head and Neck Surgery, University Hospital Hradec Králové, Králové, Czech Republic;
Institute of Clinical Biochemistry and Diagnostics, University Hospital Hradec Králové, Králové, Czech Republic.
出版信息
In Vivo. 2021 Jan-Feb;35(1):319-323. doi: 10.21873/invivo.12262.
BACKGROUND
MicroRNAs (miRNAs) are non-coding regulatory molecules 18-25 nucleotides in length that act as post-transcriptional regulators of gene expression. MiRNAs affect various biological processes including carcinogenesis. Deregulation of miRNAa expression has been described in a variety of tumors including papillary thyroid carcinoma (PTC). The aim of the present study was to investigate the role of selected miRNAs in PTC and find associations between miRNA expression and the BRAF (V600E) mutation.
MATERIALS AND METHODS
The study group comprised a total of 62 patients with surgically treated PTC. The control group consisted of 30 patients with nodular goitre that were surgically treated in the same time period. The expression status of miR-146b, miR-181a, miR-187, miR-221 and miR-222 was determined using quantitative real-time PCR. BRAF mutation analysis was performed by PCR with reverse hybridization.
RESULTS
MiR-146b, miR-181a, miR-187, miR-221 and miR-222 were up-regulated in PTC compared to normal thyroid gland tissue of the same patient. MiR-146b, miR-187, miR-221 and miR-222 were also up-regulated in PTC compared to nodular goitre. The recurrent tumors were statistically significantly associated with up-regulation of miR-221. The mutation V600E of BRAF gene was significantly associated with up-regulation of miR-146b and with down-regulation of miR-187.
CONCLUSION
Over-expression of selected miRNAs in PTC compared to normal thyroid gland tissue and nodular goitre was found. Moreover, miR-221 may serve as a prognostic marker as its over-expression was significantly associated with recurrent tumors.
背景
微小 RNA（miRNA）是一种长度为 18-25 个核苷酸的非编码调控分子，作为基因表达的转录后调控因子。miRNA 影响多种生物学过程，包括癌发生。miRNA 表达失调已在多种肿瘤中得到描述，包括甲状腺乳头状癌（PTC）。本研究旨在探讨选定 miRNA 在 PTC 中的作用，并寻找 miRNA 表达与 BRAF（V600E）突变之间的关联。
材料和方法
研究组共纳入 62 例接受手术治疗的 PTC 患者。对照组为同期手术治疗的 30 例结节性甲状腺肿患者。采用实时定量 PCR 检测 miR-146b、miR-181a、miR-187、miR-221 和 miR-222 的表达状态。采用 PCR 反向杂交法进行 BRAF 突变分析。
结果
与同一患者的正常甲状腺组织相比，PTC 中 miR-146b、miR-181a、miR-187、miR-221 和 miR-222 呈上调表达。与结节性甲状腺肿相比，PTC 中 miR-146b、miR-187、miR-221 和 miR-222 也呈上调表达。复发性肿瘤与 miR-221 的上调表达呈统计学显著相关。BRAF 基因 V600E 突变与 miR-146b 的上调表达和 miR-187 的下调表达显著相关。
结论
与正常甲状腺组织和结节性甲状腺肿相比，PTC 中选定 miRNA 的表达呈上调。此外，miR-221 可能作为一种预后标志物，因为其上调表达与复发性肿瘤显著相关。
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