RESUMO
MicroRNA-154 (miR-154) is dysregulated in some human malignancies and is correlated with tumor progression. However, its expression and function in non-small cell lung cancer (NSCLC) remain unclear. Therefore, we explored the effects of miR-154 on NSCLC tumorigenesis and development. Using quantitative reverse transcription-polymerase chain reaction, we detected miR-154 expression in NSCLC cell lines and primary tumor tissues. The association between miR-154 expression and clinicopathological factors was investigated, and the effects of miR-154 on the biological behavior of NSCLC cells were examined. Ultimately, the potential regulatory effect of miR-154 on high-mobility group A2 protein (HMGA2) expression was confirmed. miR-154 was significantly downregulated in NSCLC cell lines and clinical specimens. Reduced miR-154 expression was significantly associated with lymph node metastasis, advanced TNM stage, and shorter overall survival. Multivariate regression analysis confirmed that downregulation of miR-154 was an independent unfavorable prognostic factor for patients with NSCLC. Overexpression of miR-154 inhibited NSCLC cell proliferation, invasion, and migration, and promoted cell apoptosis in vitro. Furthermore, a luciferase reporter assay identified HMGA2 as a direct target of miR-154. Our findings indicate that miR-154 may act as a tumor suppressor in NSCLC and would serve as a novel therapeutic agent for miR-based therapy.
RESUMO
This study was performed to compare the effects of recombinant human growth hormone (rhGH), glutamine (Gln) and simultaneous treatment with rhGH and Gln in rats subjected to 75% intestinal resection and maintained with parenteral nutrition (PN) for 6 days. Morphological changes including mucosal thickness, villus height, crypt depths and villus surface area of the residue jejunum were measured under a light microscope; expression of PCNA as an index of cell proliferation and apoptotic cells were observed using immunohistochemical staining; Ileal IGF-1 mRNA was determined by Northern blot analysis. The morphological parameters of the jejunal mucosa in rats treated with PN alone were only about 52-62% of those in reference group (P<0.01), this atrophy of the jejunal mucosa was accompanied by a 2.5-fold decrease in absolute counts of PCNA and a 10-fold increase in apoptotic index (P<0.01), IGF-1 mRNA transcript in residue ileum was decreased significantly (P<0.01). However, with rhGH or Gln, the mucosal architecture was improved significantly and was further improved when rhGH and Gln were given together, the morphological values in rats treated with Gln+rhGH was 79% higher than those with PN alone, and was associated with a 2-fold increase in PCNA counts and a 4-fold decrease in apoptotic index (P<0.01), IGF-1 mRNA expression was 78% higher than those with PN alone (P<0.01). We conclude that rhGH and Gln have synergistic effects on adaptation of the intestinal remnant in parenterally fed, short-bowel rats. The underlying mechanisms are associated with increased proliferation and decreased apoptosis in the intestinal epithelial cells. Local intestinal production of IGF-1 plays an important role in adaptation of the small intestine. Our findings support the concept that specific gut-trophic nutrients and growth factors may be combined to enhance the intestinal adaptation.
