Third Department of Surgery , Tokyo Medical University, Tokyo, Japan.
Cancer Sci. 2011 Dec;102(12):2264-71. doi: 10.1111/j.1349-7006.2011.02081.x. Epub 2011 Sep 27.
MicroRNAs (miRNAs) belong to a class of endogenously expressed non-coding small RNAs that function primarily as gene regulators. Growing evidence suggests that miRNAs play a significant role in tumor development, making them potential biomarkers for cancer diagnosis and prognosis. The miR-17-92 cluster has emerged as an important locus, being highly overexpressed in several cancers in association with cancer development and progression. The miR-17-92 miRNA cluster generates a single polycistronic primary transcript that yields six mature miRNAs: miR-17, miR-18a, miR-19a, miR-20a, miR-19b, and miR-92a. In colon cancer development, the pathophysiologic roles of these transcripts and their targets are largely unknown. In the present study, we performed copy number analyses of the six miRNAs transcribed from the miR-17-92 cluster in colon tumor tissues. We determined that miR-92a was transcribed at higher levels than the other five miRNAs in both adenomas and carcinoma. In addition, miR-92a directly targeted the anti-apoptotic molecule BCL-2-interacting mediator of cell death (BIM) in colon cancer tissues. An anti-miR-92a antagomir induced apoptosis of colon cancer-derived cell lines. These data indicate that miR-92a plays a pivotal role in the development of colorectal carcinoma.
微小 RNA（miRNA）属于一类内源性表达的非编码小 RNA，主要作为基因调节剂发挥作用。越来越多的证据表明，miRNA 在肿瘤发生发展中起着重要作用，使其成为癌症诊断和预后的潜在生物标志物。miR-17-92 簇已成为一个重要的基因座，在几种癌症中高度过表达，与癌症的发生和发展有关。miR-17-92 miRNA 簇产生一个单一的多顺反子初级转录本，产生六个成熟的 miRNA：miR-17、miR-18a、miR-19a、miR-20a、miR-19b 和 miR-92a。在结肠癌的发生发展过程中，这些转录本及其靶标的病理生理作用尚不清楚。在本研究中，我们对结肠癌组织中来源于 miR-17-92 簇的六个 miRNA 的拷贝数进行了分析。我们发现，miR-92a 在腺瘤和癌组织中的转录水平均高于其他五个 miRNA。此外，miR-92a 可直接靶向结肠癌组织中的抗凋亡分子 BCL-2 相互作用介导的细胞死亡（BIM）。抗 miR-92a 反义寡核苷酸可诱导结肠癌衍生细胞系发生凋亡。这些数据表明，miR-92a 在结直肠癌的发生发展中起着关键作用。
