Department of Otolaryngology-Head and Neck Surgery, University of Washington, Seattle, Washington 98115-7744, USA.
Otolaryngol Head Neck Surg. 2012 Sep;147(3):501-8. doi: 10.1177/0194599812442490. Epub 2012 Apr 2.
To better understand possible mechanisms involved in the dysregulation of gene expression unique to oral squamous cell carcinoma (OSCC) metastasis, the investigators examined the differential expression of microRNAs (miRNAs) in OSCC metastasis and their functional impact on target gene expression.
Observational assessment of DNA copy number, miRNA, and RNA expression in primary and metastatic OSCC.
University of Washington Medical Center and affiliated hospitals.
Tumor samples were taken from patients with primary incident OSCC; cells were laser-capture microdissected from 17 nonmetastatic primary tumors and 20 metastatic lymph nodes.
DNA copy number aberrations and gene expression profiles were previously determined using Affymetrix 250K Nsp I SNP arrays and HU133 plus 2.0 expression arrays. miRNAs were interrogated with Exiqon's Ready-to-Use PCR Panels assessing the expression of 368 human miRNAs.
Investigators found 31 miRNAs differentially expressed between metastatic and nonmetastatic samples (false discovery rate <0.4; 26 overexpressed and 5 underexpressed in metastatic samples). Expression of 7 of these miRNAs was significantly associated with their DNA copy numbers, and expressions of 8 of these miRNAs were significantly associated with their target genes. Among these unique miRNAs, miR-140-3p, miR-29c, and miR-29a were differentially expressed in metastasis versus nonmetastatic samples and had a strong positive correlation with their DNA copy numbers and a negative correlation with the expression of their target genes.
Results suggest that DNA copy number aberration may play a role in the dysregulation of some differentially expressed miRNAs in OSCC metastasis, warranting further investigation.
为了更好地理解口腔鳞状细胞癌（OSCC）转移所特有的基因表达失调的可能机制，研究者检测了 OSCC 转移中差异表达的 microRNAs（miRNAs）及其对靶基因表达的功能影响。
对原发性和转移性 OSCC 中的 DNA 拷贝数、miRNA 和 RNA 表达进行观察性评估。
华盛顿大学医学中心及其附属医院。
从原发性 OSCC 患者中获取肿瘤样本；从 17 个非转移性原发性肿瘤和 20 个转移性淋巴结中使用激光捕获微切割获取细胞。
DNA 拷贝数异常和基因表达谱先前使用 Affymetrix 250K Nsp I SNP 阵列和 HU133 plus 2.0 表达阵列确定。使用 Exiqon 的 Ready-to-Use PCR Panels 检测 368 个人类 miRNA 的表达情况来检测 miRNAs。
研究者发现 31 个 miRNA 在转移性和非转移性样本之间表达差异（错误发现率<0.4；26 个在转移性样本中过表达，5 个在转移性样本中低表达）。这些 miRNA 中的 7 个的表达与其 DNA 拷贝数显著相关，并且这些 miRNA 中的 8 个的表达与其靶基因显著相关。在这些独特的 miRNA 中，miR-140-3p、miR-29c 和 miR-29a 在转移性与非转移性样本中表达差异，并且与它们的 DNA 拷贝数呈正相关，与它们的靶基因的表达呈负相关。
结果表明，DNA 拷贝数异常可能在 OSCC 转移中一些差异表达 miRNA 的失调中起作用，值得进一步研究。
