Department of Biomedical Informatics, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
J Gastrointest Surg. 2012 May;16(5):905-12; discussion 912-3. doi: 10.1007/s11605-011-1815-0. Epub 2012 Feb 24.
Altered expression of specific microRNAs (miRNA) is known to occur during colorectal carcinogenesis. However, little is known about the genome-wide alterations in miRNA expression during the neoplastic progression of primary colorectal cancers.
Using a miRNA array platform, we evaluated the expression of 668 miRNA in primary colonic adenocarcinomas. Biological functions of selected miRNA were evaluated with in vitro invasion assays.
RNA was extracted for miRNA analysis from 65 primary colon cancers. We identified a seven-miRNA expression signature that differentiated stage I and stage IV primary colon cancers. We then demonstrated this signature was able to discriminate between stage II and III primary colon cancers. Six differentially expressed miRNA were downregulated in association with the development of metastases, and all 7 miRNA were complementary strand miRNA. We transfected HCT-116, a highly invasive colon cancer cell line, with corresponding downregulated miRNA and demonstrated that overexpression of three miRNA (miR200c*, miR143*, and miR424*) significantly abrogated invasive potential.
We have identified a seven-miRNA signature that is associated with metastatic potential in the primary tumor. Forced overexpression of three downregulated miRNA resulted in attenuation of in vitro invasion, suggesting direct tumor suppressive function and further supporting the biological importance of complementary strand miRNA.
已知特定 microRNA（miRNA）的表达改变发生在结直肠癌的发生过程中。然而，对于原发性结直肠癌肿瘤进展过程中 miRNA 表达的全基因组改变知之甚少。
我们使用 miRNA 阵列平台评估了 668 种 miRNA 在原发性结肠腺癌中的表达。通过体外侵袭实验评估选定 miRNA 的生物学功能。
从 65 例原发性结肠癌中提取了 miRNA 分析用的 RNA。我们确定了一个能够区分 I 期和 IV 期原发性结肠癌的七 miRNA 表达特征。然后，我们证明该特征能够区分 II 期和 III 期原发性结肠癌。与转移发展相关的 6 个差异表达 miRNA 下调，所有 7 个 miRNA 均为互补链 miRNA。我们用相应的下调 miRNA 转染高侵袭性结肠癌细胞系 HCT-116，结果表明，过表达三种 miRNA（miR200c*、miR143和 miR424）显著抑制了侵袭潜能。
我们已经确定了一个与原发性肿瘤转移潜能相关的七 miRNA 特征。强制过表达三种下调 miRNA 导致体外侵袭能力减弱，表明其具有直接的肿瘤抑制功能，进一步支持互补链 miRNA 的生物学重要性。
