Differential Expression of MicroRNAs in Papillary Thyroid Carcinoma and Their Role in Racial Disparity.
Differential Expression of MicroRNAs in Papillary Thyroid Carcinoma and Their Role in Racial Disparity.
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DOI：
10.4172/1948-5956.1000340
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发表时间：
2015-05
期刊：
影响因子：
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通讯作者：
Sarkar FH
中科院分区：
文献类型：
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作者：
Suresh R;Sethi S;Ali S;Giorgadze T;Sarkar FH
微小RNA（microRNAs，miRNAs）在甲状腺乳头状癌（papillary thyroid cancer，PTC）的诊断和预后中发挥重要作用，并可用于靶向治疗。然而，目前还没有研究表明miRNA表达存在种族差异，这可以解释PTC患者的总生存率差异。主要种族群体中miRNAs的表达分析对于优化个性化治疗策略将是重要的。在目前的研究中，我们评估了8种miRNA在正常和肿瘤组织中的差异表达，并评估了非洲裔美国人（AA）和高加索裔美国人（CA）之间的种族差异。首先，使用含有超过70%肿瘤细胞的福尔马林固定石蜡包埋（FFPE）肿瘤组织切片进行miRNA表达谱分析。对AA和CA患者的正常和肿瘤甲状腺组织切片进行了研究。使用miRBase版本18（LC Sciences，Houston，TX，USA）进行miRNA微阵列分析。使用定量实时PCR（qRT-PCR）来验证8种选择的miRNA的表达。抗肿瘤途径分析显示Ras和NF-κB B等靶基因参与了抗肿瘤作用。发现两个种族之间失调的miRNA如miR-221和miR-31具有统计学显著性。使用qRT-PCR，我们发现与正常组织相比，miR-21，miR-146 b，miR-221，miR-222，miR-31和miR-3613在肿瘤中上调，而miR-138和miR-98下调。虽然样本量很小，但我们发现了几种失调的miRNA具有种族差异。miRNAs的差异表达表明，这些miRNAs及其靶基因可能有助于进一步了解PTC的机制及其临床意义，包括miRNAs替代治疗或其敲除策略。
MicroRNAs (miRNAs) are known to play important roles in the diagnosis and prognosis of papillary thyroid cancer (PTC), and they are useful in developing targeted therapies. However, there have been no studies on the existence of racial differences in miRNAs expression that could explain differential overall survival of PTC patients. Expression analysis of miRNAs in major racial groups would be important for optimizing personalized treatment strategies. In the current study, we assessed the differential expression of 8 miRNAs between normal and tumor tissues, and also assessed racial differences between African American (AA) and Caucasian American (CA). First, the miRNA expression profiling was performed using formalin-fixed paraffin embedded (FFPE) tissue sections of tumor containing over 70% tumor cells. Normal and tumor sections of thyroid tissues were studied from AA and CA patients. The miRNA microarray profiling was done using miRBase version 18 (LC Sciences, Houston, TX, USA). Quantitative real-time PCR (qRT-PCR) was used to validate expression of 8 selected miRNAs. Ingenuity pathway analysis showed involvement of target genes, such as Ras and NF-κB. Deregulated miRNAs such as miR-221 and miR-31 were found to be statistically significant between the two races. Using qRT-PCR, we found that miR-21, miR-146b, miR-221, miR-222, miR-31, and miR-3613 were up-regulated while miR-138 and miR-98 were down-regulated in tumors compared to normal tissues. Though sample size was small, we found several deregulated miRNAs having racial differences. The differential expression of miRNAs suggest that these miRNAs and their target genes could be useful to gain further mechanistic insight of PTC and their clinical implications, including miRNA replacement therapy or their knockdown strategies.