Purpose: To quantify the expression of miR-497 and its target gene VEGF-B in patients with hepatocellular carcinoma (HCC), and microvascular invasion (MVI) to identify their relationship with clinicopathological characteristics and prognosis.
Methods: Imaging data of postoperative cancer and adjacent tissues of HCC patients with MVI diagnosed by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) were retrospectively analyzed. The expression of miR-497 in clinical samples and HepG2 and SMMC-7721 cell lines was quantified by quantitative PCR (Q-PCR). Correlations between miR-497 and patient survival and VEGF-B were explored in TCGA database. The invasion and migration of SMMC-7721 cells were tested by transwell assay. The binding sites between miR-497 and its target gene VEGF-B were verified by dual-luciferase reporter (DLR) assay, and VEGF-B levels were analyzed by western blot (WB).
Results: miR-497 showed a lower expression in HCC patients with MVI than those without MVI. It was also lowly expressed in HCC cell lines compared to normal liver cell lines. The proliferation and migration in HCC cells were inhibited by overexpression of miR-497, which were enhanced after transfection with miR-497 inhibitor. miR-497 had an effect on VEGF-B levels and there was a regulatory relationship between them. miR-497 was able to target VEGF-B and downregulate the receptor of VEGF-B (FLT-1).
Conclusion: miR-497 was lowly expressed in HCC tissues, and its overexpression inhibited invasion and metastasis in HCC cells by suppressing VEGF-B levels. MiR-497 and its target gene VEGF-B are closely associated with the biological function and may serve as prognostic factors of MVI in patients with HCC.