MicroRNA profiling of Barrett's oesophagus and oesophageal adenocarcinoma
MicroRNA profiling of Barrett's oesophagus and oesophageal adenocarcinoma
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DOI：
10.1002/bjs.7000
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发表时间：
2010-06-01
影响因子：
9.6
通讯作者：
Michael, M. Z.
中科院分区：
文献类型：
--
作者：
Wijnhoven, B. P. L.;Hussey, D. J.;Michael, M. Z.
背景资料：促使食管鳞状上皮化生向肠化生和腺癌发展的基因变化尚不清楚。microRNA（miRNAs）的异常表达参与了癌症的发生。本研究探讨是否miRNAs发挥作用的发展oesophageal adenocarcinoma.Methods：RNA提取正常食管鳞状上皮，正常胃上皮，Barrett食管肠上皮化生和oesophageal adenocarcinoma从16个人获得的粘膜。通过微阵列分析确定了377种人类miRNAs的表达谱，并使用实时逆转录聚合酶链反应（RT-PCR）在32个individual.Results组织中进一步分析了选定的miRNAs。其中，选择miR-21、miR-143、miR-145、miR-194、miR-203、miR-205和miR-215用于通过实时RT-PCR进行验证。结果发现，miR-21、miR-143、miR-145、miR-194和miR-215在柱状上皮中的表达显著高于正常鳞状上皮。miR-143、miR-145和miR-215在食管腺癌中的表达低于Barrett食管。miR-203和miR-205的水平在正常鳞状上皮中高，而在柱状上皮中低。miR-205在胃粘膜上皮中的表达水平低于Barrett食管和腺癌。结论：miRNA的表达可能是食管上皮疾病的标志。特异性miRNAs的失调可能导致食管粘膜的化生和肿瘤过程。
Background: The genetic changes that drive metaplastic progression from squamous oesophageal mucosa toward intestinal metaplasia and adenocarcinoma are unclear. The aberrant expression of microRNAs (miRNAs) is involved in the development of cancer. This study examined whether miRNAs play a role in the development of oesophageal adenocarcinoma.Methods: RNA was extracted from mucosa of normal oesophageal squamous epithelium, normal gastric epithelium, Barrett's oesophagus with intestinal metaplasia and oesophageal adenocarcinoma obtained from 16 individuals. Expression profiles of 377 human miRNAs were determined by microarray analysis and selected miRNAs were analysed further using real-time reverse transcription polymerase chain reaction (RT-PCR) in tissues from 32 individuals.Results: Microarray analyses identified 44 miRNAs likely to have altered expression between various mucosal samples. Of these, miR-21, miR-143, miR-145, miR-194, miR-203, miR-205 and miR-215 were chosen for validation by real-time RT-PCR. Tissue-specific expression profiles were observed, with miR-21, miR-143, miR-145, miR-194 and miR-215 significantly upregulated in columnar tissues compared with normal squamous epithelium. Expression of miR-143, miR-145 and miR-215 was lower in oesophageal adenocarcinoma than in Barrett's oesophagus. Levels of miR-203 and miR-205 were high in normal squamous epithelium and low in columnar epithelia. MiR-205 levels were lower in gastric epithelium than in both Barrett's oesophagus and adenocarcinoma.Conclusion: Expression of miRNA might define disease states in oesophageal epithelium. Dysregulation of specific miRNAs could contribute to metaplastic and neoplastic processes in the oesophageal mucosa.