López-Urrutia Eduardo, Coronel-Hernández Jossimar, García-Castillo Verónica, Contreras-Romero Carlos, Martínez-Gutierrez Antonio, Estrada-Galicia Diana, Terrazas Luis Ignacio, López-Camarillo César, Maldonado-Martínez Hector, Jacobo-Herrera Nadia, Pérez-Plasencia Carlos
1 Laboratorio de Genómica Funcional, Unidad de Biomedicina, Facultad de Estudios Superiores (FES) Iztacala, Universidad Nacional Autónoma de México (UNAM), Tlalnepantla, México.
2 Laboratorio de Inmunología, Facultad de Estudios Superiores (FES) Iztacala, Universidad Nacional Autónoma de México (UNAM), Tlalnepantla, Mexico.
Tumour Biol. 2017 Apr;39(4):1010428317695945. doi: 10.1177/1010428317695945.
MicroRNAs are non-coding short RNAs that target the 3' untranslated region of messenger RNAs (mRNAs) and lead to their degradation or to translational repression. Several microRNAs have been designated as oncomirs, owing to their regulating tumor suppressor genes. Interestingly, a few of them have been found to target multiple genes whose simultaneous suppression contributes to the development of a tumoral phenotype. Here, we have showed that miR-26a is overexpressed in colorectal cancer data obtained from TCGA Research Network and in human colon cancer pathological specimens; moreover, an orthotopic in vivo model of colon cancer showed overexpression of miR-26a, while Rb1 expression inversely correlated to miR-26a in TCGA Research Network data, pathological samples, and the in vivo model. Then, by means of luciferase assay, we demonstrated that miR-26a targets the 3' untranslated region of Rb1 mRNA directly. This is, to our knowledge, the first report of miR-26a targeting Rb1 in colon cancer. The results of this study suggested that miR-26a could serve as a progression biomarker in colorectal cancer. Further validation studies are still needed to confirm our findings.
微小RNA是一类非编码短RNA,其靶向信使RNA(mRNA)的3'非翻译区,导致其降解或翻译抑制。由于其对肿瘤抑制基因的调控作用,几种微小RNA已被指定为致癌miRNA。有趣的是,其中一些已被发现靶向多个基因,这些基因的同时抑制有助于肿瘤表型的发展。在这里,我们已经表明,miR-26a在从TCGA研究网络获得的结直肠癌数据和人类结肠癌病理标本中过表达;此外,结肠癌的原位体内模型显示miR-26a过表达,而在TCGA研究网络数据、病理样本和体内模型中,Rb1表达与miR-26a呈负相关。然后,通过荧光素酶测定,我们证明miR-26a直接靶向Rb1 mRNA的3'非翻译区。据我们所知,这是miR-26a在结肠癌中靶向Rb1的首次报道。本研究结果表明,miR-26a可能作为结直肠癌进展的生物标志物。仍需要进一步的验证研究来证实我们的发现。