MicroRNA expression in ileal carcinoid tumors: downregulation of microRNA-133a with tumor progression.
MicroRNA expression in ileal carcinoid tumors: downregulation of microRNA-133a with tumor progression.
复制标题
DOI：
10.1038/modpathol.2009.161
复制
发表时间：
2010-03
期刊：
影响因子：
--
通讯作者：
中科院分区：
文献类型：
--
作者：
微小RNA（MicroRNAs）参与细胞增殖、分化和凋亡，并且可作为肿瘤抑制基因或癌基因发挥作用。微小RNA在神经内分泌肿瘤（如回肠类癌）中的作用在很大程度上尚不明确。我们使用QuantiMir系统通过逆转录聚合酶链反应（RT - PCR）检测了来自回肠的8对原发和转移性类癌肿瘤中95种微小RNA的差异表达。选择用于QuantiMir系统芯片的所有微小RNA都是基于它们与癌症生物学、细胞发育和凋亡相关的潜在功能。样本中微小RNA的表达以微小RNA - 197为参照进行标准化，并对匹配的原发和转移性肿瘤进行了比较。在所有原发和匹配的转移性肿瘤样本之间，微小RNA - 133a、145、146、222和10b均下调，并且在8个转移性类癌中的6个与原发肿瘤相比，微小RNA - 183、488和19a + b上调。通过TaqMan实时逆转录聚合酶链反应和Northern杂交对微小RNA - 133a进行了进一步分析，使用了另外6对匹配的原发和转移性样本，结果支持了聚合酶链反应芯片的发现。在8例原始病例中，与原发肿瘤相比，转移性肿瘤中微小RNA - 133a的表达存在显著差异且下调（p < 0.009），在用于验证的另外6例中也是如此（p < 0.014）。使用正常回肠进行激光捕获显微切割和实时逆转录聚合酶链反应分析发现，正常肠嗜铬细胞中存在微小RNA - 133a的表达。在正常回肠中的原位杂交显示，一些黏膜内分泌细胞表达微小RNA - 133a。通过原位杂交，原发和转移性回肠类癌肿瘤均表达微小RNA - 133a。这些结果提供了有关新型标志物微小RNA的信息，这些微小RNA可能用作肠道类癌肿瘤的生物标志物和/或治疗靶点。
MicroRNAs are involved in cell proliferation, differentiation, and apoptosis and can function as tumor suppressor genes or oncogenes. The role of microRNAs in neuroendocrine tumors such as ileal carcinoids is largely unknown. We examined the differential expression of 95 microRNAs by RT-PCR using the QuantiMir System in eight matching primary and metastatic carcinoid tumors from the ileum. All microRNAs chosen for the QuantiMir System Array were based on their potential functions related to cancer biology, cell development and apoptosis. The expression of microRNAs for the samples was normalized to microRNA-197, and the matching primary and metastatic tumors were compared. There was down-regulation of microRNA-133a, 145, 146, 222 and 10b in all samples between the primary and matching metastatic tumors and up-regulation of microRNA-183, 488 and 19a + b in six of eight metastatic carcinoids compared to the primary tumors. MicroRNA-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 microRNA-133a expression with down-regulation 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 microRNA-133a expression in normal enterochromaffin cells. In situ hybridization in normal ileum showed that some of the mucosal endocrine cells expressed microRNA-133a. Both primary and metastatic ileal carcinoid tumors expressed microRNA-133a by in situ hybridization. These results provide information about novel marker microRNAs that may be used as biomarkers and/or therapeutic targets in intestinal carcinoid tumors.
登录
查看更多内容
影响因子：
11.2
作者：
Hurst DR;Edmonds MD;Scott GK;Benz CC;Vaidya KS;Welch DR
通讯作者：
Welch DR
影响因子：
5.8
作者：
Modlin, Irvin M.;Kidd, Mark;Champaneria, Manish C.
通讯作者：
Champaneria, Manish C.
影响因子：
3.1
作者：
NILSSON, O;WANGBERG, B;AHLMAN, H
通讯作者：
AHLMAN, H
影响因子：
3.3
作者：
McCarthy, John J.;Esser, Karyn A.
通讯作者：
Esser, Karyn A.
影响因子：
2.2
作者：
Schwertheim, S.;Sheu, S-Y.;Schmid, K. W.
通讯作者：
Schmid, K. W.