RESUMEN
MicroRNAs (miRNA) are small noncoding RNAs that regulate gene expression in human diseases, including lung cancer. miRNAs have oncogenic and nononcogenic functions in lung cancer. In this study, we report the identification of a novel miRNA, miR-7515, from lung cancer cells. The novel miR-7515 was characterized using various predictive programs and experimental methods. miR-7515 was able to forming a stem-loop structure and its sequence was conserved in mammals. The expression level of miR-7515 in lung cancer cells and tissues was profiled using TaqMan miRNA assays. miR-7515 was downregulated in lung cancer compared with normal human lung cells and tissues. The target of miR-7515 was determined using a dual luciferase reporter assay. Expression of the target gene was determined by quantitative RT-PCR and Western blot analysis after transfection with miR-7515. miR-7515 directly suppressed human mesenchymal-epithelial transition factor (c-Met) by binding to the 3' untranslated region (UTR). Overexpression of miR-7515 significantly decreased cell-cycle-related proteins downstream of c-Met through c-Met inhibition. Cell proliferation and migration were examined using the XTT proliferation assay and the Transwell migration assay. miR-7515 led to decreased cell proliferation, migration and invasion in a lung cancer cell line. These results suggest that miR-7515 plays an important role in the proliferation and migration of lung cancer cells through c-Met regulation.
Asunto(s)
Movimiento Celular/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , MicroARNs/metabolismo , Procesos de Crecimiento Celular/genética , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Pulmonares/metabolismo , MicroARNs/genética , TransfecciónRESUMEN
MicroRNAs (miRNAs) are small non-coding RNAs that regulate diverse biological processes. We cloned novel small RNA from human mesenchymal stem cells (hMSCs) and termed microRNA-5787 (hsa-miR-5787) that met the criteria for a miRNA. The level of miR-5787 was elevated in senescent fibroblasts. Based on the target prediction algorithm and results that were obtained, we find that eukaryotic translation initiation factor 5 (eIF5) is a target of miR-5787. Similar to the over-expression of miR-5787, we showed that repression of eIF5 in fibroblasts negatively affected cell growth. Therefore, we propose that the miR-5787 represses cell growth, in part, by targeting eIF5.
