Department of Histopathology, Sir Patrick Dun Research Laboratory, Trinity College Dublin, St. James' Hospital Dublin, Ireland.
Front Endocrinol (Lausanne). 2012 Sep 3;3:102. doi: 10.3389/fendo.2012.00102. eCollection 2012.
MicroRNAs (miRNAs) are small non-coding RNAs approximately 22 nucleotides in length that function as regulators of gene expression. Dysregulation of miRNAs has been associated with initiation and progression of oncogenesis in humans. Our group has previously described a unique miRNA expression signature, including the MIR200 family member MIR141, which can differentiate papillary thyroid cancer (PTC) cell lines from a control thyroid cell line. An investigation into the expression of MIR141 in a series of archival thyroid malignancies [n = 140; classic PTC (cPTC), follicular variant PTC, follicular thyroid carcinoma, Hashimoto thyroiditis (HT), or control thyrocytes] was performed. Each cohort had a minimum of 20 validated samples surgically excised within the period 1980-2009. A subset of the HT and cPTC cohorts (n = 3) were also analyzed for expression of TGFβR1, a key member of the TGFβ pathway and known target of MIR141. Laser capture microdissection was used to specifically dissect target cells from formalin-fixed paraffin-embedded archival tissue. Thyrocyte- and lymphocyte-specific markers (TSHR and LSP1, respectively), confirmed the integrity of cell populations in the HT cohort. RNA was extracted and quantitative RT-PCR was performed using comparative CT (ΔΔCT) analysis. Statistically significant (p < 0.05) differential expression profiles of MIR141 were found between tissue types. HT samples displayed significant downregulation of MIR141 compared to both cPTC and control thyrocytes. Furthermore, TGFβR1 expression was detected in cPTC samples but not in HT thyrocytes. It is postulated that the downregulation of this miRNA is due, at least in part, to its involvement in regulating the TGFβ pathway. This pathway is exquisitely involved in T-cell autoimmunity and has previously been linked with HT. In conclusion, HT epithelium can be distinguished from cPTC epithelium and control epithelium based on the relative expression of MIR141.
微小 RNA（miRNAs）是一种大约 22 个核苷酸长的非编码小 RNA，作为基因表达的调节剂发挥作用。miRNAs 的失调与人类肿瘤发生的起始和进展有关。我们的研究小组之前描述了一个独特的 miRNA 表达特征，包括 MIR200 家族成员 MIR141，可以将甲状腺癌（PTC）细胞系与对照甲状腺细胞系区分开来。对一系列存档甲状腺恶性肿瘤 [n=140；经典 PTC（cPTC）、滤泡状变体 PTC、滤泡状甲状腺癌、桥本甲状腺炎（HT）或对照甲状腺细胞] 中 MIR141 的表达进行了研究。每个队列都有至少 20 个在 1980-2009 年期间手术切除的验证样本。HT 和 cPTC 队列的一部分（n=3）还分析了 TGFβR1 的表达，TGFβ 途径的关键成员和 MIR141 的已知靶标。激光捕获显微切割用于从福尔马林固定石蜡包埋的存档组织中专门分离靶细胞。甲状腺细胞和淋巴细胞特异性标志物（TSHR 和 LSP1）分别证实了 HT 队列中细胞群体的完整性。提取 RNA 并使用比较 CT（ΔΔCT）分析进行定量 RT-PCR。发现组织类型之间 MIR141 的表达存在显著差异（p<0.05）。与 cPTC 和对照甲状腺细胞相比，HT 样本中 MIR141 的表达显著下调。此外，在 cPTC 样本中检测到 TGFβR1 的表达，但在 HT 甲状腺细胞中未检测到。据推测，这种 miRNA 的下调至少部分归因于其参与调节 TGFβ 途径。该途径在 T 细胞自身免疫中非常重要，并且之前与 HT 有关。总之，HT 上皮细胞可以根据 MIR141 的相对表达与 cPTC 上皮细胞和对照上皮细胞区分开来。
