MiR-92a promotes the invasion and migration of colorectal cancer by targeting RECK.

The up-regulation of miR-92a in human cancer happens frequently, and is related to an increase of metastasis and decreased survival. However, its functions in colorectal cancer (CRC) are largely unknown. This study aimed to investigate the regulatory effect of miR-92a on cell invasion and migration in colorectal cancer (CRC). A total of 158 patients with CRC were included, and in situ hybridization was used to predict the expression of miR-92a in the paraffin sections from the patients. Quantitative reverse transcription PCR was used to detect the expression of miR-92a and its target gene. Protein levels were determined by western blotting. Luciferase assays confirmed the direct target of miR-92a. Furthermore, cell invasion and migration were detected using Transwell and wound healing assays. The expression level of miR-92a in tumor tissues was upregulated compared with that of paired normal tissues and negatively correlated with the RECK protein level. The 3-year disease-free survival (DFS) and overall survival (OS) rates of miR-92a expression in the high group were significantly lower than those in the miR-92a-low group. The RECK 3'-UTR reporter activity assay suggested that the RECK gene was a direct target of miR-92a. After transfection of the miR-92a-mimic, the miR-92a levels were increased in HCT116 and SW620 cell lines, while the protein expression of RECK was decreased instead of the mRNA level, along with downregulation of matrix metalloproteinase (MMP) protein expression. Conversely, after transfection with miR-92a-inhibitor, the opposite trend was achieved. In conclusion, miR-92a promotes the invasion and migration of CRC through the RECK-MMP signaling pathway, and the upregulation of miR-92a was associated with poor long-term prognosis in CRC.

P38 MAPK signaling pathway mediates advanced oxidation protein product-induced epithelial-to-mesenchymal transition in tubular cells / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate whether the p38 mitogen-activated protein kinase (MAPK) signaling pathway mediates advanced oxidation protein products (AOPPs)-induced epithelial-to-mesenchymal transition (EMT) in tubular cells.</p><p><b>METHODS</b>Human proximal tubular cells (HK-2 cells) exposed to AOPP-bovine serum albumin (BSA) were examined for expressions of p38 MAPK and phosphorylated p38 MAPK using Western blotting. Western blotting and quantitative RT-PCR were used to examine the protein and mRNA expressions of EMT markers E-cadherin and vimentin and endoplasmic reticulum stress marker glucose-regulated protein (GRP) 78 in cells treated with SB203580 (an inhibitor of the p38 MAPK signaling pathway) prior to AOPP exposure. The cells treated with AOPPs following pretreatment with salubrinal (an inhibitor of endoplasmic reticulum stress) were also examined for expressions of p38 MAPK and phosphorylated p38 MAPK.</p><p><b>RESULTS</b>AOPP treatment induced the phosphorylation of p38 MAPK in HK-2 cells. AOPP-induced decrease in E-cadherin expression and overexpression of vimentin and GRP78 were partly inhibited by pretreatment of the cells with SB203580. Salubrina partly suppressed AOPP-induced phosphorylation of p38 MAPK in the cells.</p><p><b>CONCLUSION</b>p38 MAPK signaling pathway, which is regulated by endoplasmic reticulum stress, might mediate AOPP-induced EMT in HK-2 cells.</p>