Division of Anatomic Pathology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, USA.
Mod Pathol. 2010 Mar;23(3):367-75. doi: 10.1038/modpathol.2009.161. Epub 2009 Dec 25.
MicroRNAs (miRNAs) are involved in cell proliferation, differentiation, and apoptosis and can function as tumor suppressor genes or oncogenes. The role of miRNAs in neuroendocrine tumors such as ileal carcinoids is largely unknown. We examined the differential expression of 95 miRNAs by RT-PCR using the QuantiMir System in eight matching primary and metastatic carcinoid tumors from the ileum. All miRNAs chosen for the QuantiMir System array were based on their potential functions related to cancer biology, cell development, and apoptosis. The expression of miRNAs for the samples was normalized to miRNA-197, and the matching primary and metastatic tumors were compared. There was downregulation of miRNA-133a, -145, -146, -222, and -10b in all samples between the primary and matching metastatic tumors and upregulation of miRNA-183, -488, and -19a+b in six of eight metastatic carcinoids compared to the primary tumors. miRNA-133a was further analyzed by TaqMan real-time RT-PCR and northern hybridization using six additional matching primary and metastatic samples, which supported the PCR array findings. There were significant differences in miRNA-133a expression with downregulation in the metastasis compared to the primary in the eight original cases (P<0.009) and in the six additional cases used for validation (P<0.014). Laser capture microdissection and real-time RT-PCR analysis using normal ileum found miRNA-133a expression in normal enterochromaffin cells. In situ hybridization in normal ileum showed that some of the mucosal endocrine cells expressed miRNA-133a. Both primary and metastatic ileal carcinoid tumors expressed miRNA-133a by in situ hybridization. These results provide information about novel marker miRNAs that may be used as biomarkers and/or therapeutic targets in intestinal carcinoid tumors.
微小 RNA（miRNA）参与细胞增殖、分化和凋亡，可作为肿瘤抑制基因或癌基因发挥作用。miRNA 在神经内分泌肿瘤（如回肠类癌）中的作用尚不清楚。我们采用 RT-PCR 法（使用 QuantiMir 系统）检测了 8 例来自回肠的原发性和转移性类癌的 95 种 miRNA 的差异表达。QuantiMir 系统芯片中选择的所有 miRNA 都是基于它们在癌症生物学、细胞发育和凋亡方面的潜在功能。用 miRNA-197 对样本 miRNA 的表达进行标准化，并对原发性和转移性肿瘤进行比较。所有样本中 miRNA-133a、-145、-146、-222 和 -10b 在原发性和匹配的转移性肿瘤之间下调，而在 8 例转移性类癌中的 6 例与原发性肿瘤相比，miRNA-183、-488 和 -19a+b 上调。用 TaqMan 实时 RT-PCR 和 Northern 杂交对另外 6 例原发性和转移性匹配样本进行了 miRNA-133a 的进一步分析，支持了 PCR 芯片的发现。在 8 例原始病例中，与原发性肿瘤相比，转移性肿瘤中 miRNA-133a 的表达明显下调（P<0.009），在用于验证的 6 例病例中也有同样结果（P<0.014）。用正常回肠进行的激光捕获显微切割和实时 RT-PCR 分析发现，正常肠嗜铬细胞中存在 miRNA-133a 的表达。正常回肠的原位杂交显示，一些黏膜内分泌细胞表达 miRNA-133a。原发性和转移性回肠类癌肿瘤均通过原位杂交表达 miRNA-133a。这些结果提供了关于新型标记 miRNA 的信息，这些 miRNA 可能作为肠道类癌肿瘤的生物标志物和/或治疗靶点。
