MiRNA-92a Promote Angiogenesis in Colorectal Cancer by Inhibiting the Expression of PTEN
Abstract Background: The microRNA (miRNA) miRNA-92a has been implicated in colorectal cancer (CRC) pathology. Methods: Here, we examined miRNA-92a involvement in CRC-associated angiogenesis, including examining a mechanism by which miRNA-92a may exert such effects. MiRNA-92a expression in 25 clinical CRC samples and in HT29, SW620, SW480 and HCT116 CRC cells was detected with quantitative real-time polymerase chain reaction (qRT-PCR). Blood microvessels were labeled by immunohistochemistry (IHC) with an anti-CD31 antibody. MiR-92a mimic or inhibitor were transfected into HCT116 and SW620 cells to up- and down-regulate miRNA-92a expression, respectively. The effects of altering miRNA-92a expression levels on HUVEC (human umbilical vein endothelial cell) tubule formation and PTEN protein expression were measured. Results: MiRNA-92a was more highly expressed in CRC tissues and cell lines than in matched adjacent tissues (p <0.01) and normal epithelial cells (p <0.05), respectively. Microvessel density (MVD) was elevated in CRC tissues relative to adjacent tissues (p <0.01), and miRNA-92a levels correlated with MVDs in CRC tissues (Pearson coefficient r = 0.580, p = 0.01). The cells culture supernatant of CRC cell with miRNA-92a overexpression (or suppression) can promoted (or reduced) the formation of HUVEC tubules (P <0.05). Elevated miRNA-92a expression was associated with reduced PTEN expression in CRC cells (p <0.01). Conclusion: Modulation of miR-92a, which is highly expressed in CRC cells and tissues, is associated directly with differences in CRC angiogenesis. MiR-92a could promote tumor angiogenesis in CRC by inhibiting the expression of PTEN.