关键词: BRAF histological variant hobnail miR-146 miR-205 miR-21 microRNA papillary thyroid cancer

Mesh : Carcinoma, Papillary / genetics pathology Humans MicroRNAs / metabolism Proto-Oncogene Proteins B-raf / genetics Thyroid Cancer, Papillary / genetics Thyroid Neoplasms / diagnosis genetics metabolism

来  源:   DOI:10.3389/fendo.2022.834075   PDF(Pubmed)

Abstract:
Papillary thyroid carcinoma (PTC) is a miscellaneous disease with a variety of histological variants, each with its own mutational profile, and clinical and prognostic characteristics. Identification of microRNA (miRNA) expression profiles represents an important benchmark for understanding the molecular mechanisms underlying the biological behavior of these unique PTC subtypes in order that they be better characterized. We considered a series of 35 PTC samples with a histological diagnosis of either hobnail (17 cases) or classical variant (nine cases) and with a specific BRAF p.K601E mutation (nine cases). We determined the overall miRNA expression profile with NanoString technology, and both quantitative reverse transcription-PCR and in situ hybridization were used to confirm selected miRNAs. The miRNA signature was found to consistently differentiate specific histotypes and mutational profiles. In contrast to the BRAF p.K601E mutation and classic PTCs, three miRNAs (miR-21-5p, miR-146b-5p, and miR-205-5p) were substantially overexpressed in the hobnail variant. The current study found that different miRNA signature profiles were linked to unique histological variants and BRAF mutations in PTC. Further studies focusing on the downstream pathogenetic functions of mRNAs in thyroid neoplasms are warranted.
摘要:
甲状腺乳头状癌(PTC)是一种具有多种组织学变异的杂病,每个都有自己的突变特征,以及临床和预后特征。微RNA(miRNA)表达谱的鉴定代表了理解这些独特PTC亚型生物学行为的分子机制的重要基准,以便更好地表征它们。我们考虑了一系列35个PTC样本,其组织学诊断为hobnail(17例)或经典变体(9例),并且具有特定的BRAFp.K601E突变(9例)。我们使用NanoString技术确定了总体miRNA表达谱,定量逆转录PCR和原位杂交用于确认选择的miRNA。发现miRNA特征一致地区分特定的组织型和突变谱。与BRAFp.K601E突变和经典PTC相比,三个miRNA(miR-21-5p,miR-146b-5p,和miR-205-5p)在hobnail变体中基本上过表达。目前的研究发现,不同的miRNA特征谱与PTC中独特的组织学变异和BRAF突变有关。需要进一步研究甲状腺肿瘤中mRNA的下游致病功能。
公众号