MiR-497 suppresses angiogenesis and metastasis of hepatocellular carcinoma by inhibiting VEGFA and AEG-1

Abstract

Hepatocellular carcinoma (HCC) is a worldwide malignance and displays marked vascular abnormalities and active metastasis. MicroRNAs (miRNAs) have been shown to play important roles in regulating tumor properties in cancer, however, whether miR-497 contributes to HCC angiogenesis or metastasis remains unclear. In this study, we found that miR-497 was significantly down-regulated in HCC tissue samples and cell lines. Gain-of-function and loss-of-function studies revealed that miR-497 could repress both the pro-angiogenic and metastatic ability of HCC cells. Subsequent investigations disclosed that miR-497 directly inhibited the 3′-untranslated regions (UTRs) of vascular endothelial growth factor A (VEGFA) and astrocyte elevated gene-1 (AEG-1). Furthermore, overexpression of these targets antagonized the function of miR-497. Based on nude mouse models, we demonstrated that overexpression of miR-497 significantly repressed microvessel densities in xenograft tumors and reduced pulmonary metastasis. In conclusion, our findings indicate that miR-497 downregulation contributes to angiogenesis and metastasis in HCC.

MiR-497∼195 cluster regulates angiogenesis during coupling with osteogenesis by maintaining endothelial Notch and HIF-1α activity

“…miR-497 and miR-195 belong to miR-15 family, It has been reported that miR-497∼195 negatively regulates angiogenesis in tumours21222324. Almeida et al .…”

miRNA-205 targets VEGFA and FGF2 and regulates resistance to chemotherapeutics in breast cancer

“…57 Beside promoting resistance to imatinib in chronic myeloid leukemia 36 and promoting resistance to gefitinib in non-small cell lung cancer, 35 FGF2 expression is also a stronger predictor of paclitaxel resistance than P-gp, p53 or Bcl-2 in several cancers. 58 Several VEGFA-/FGF2-targeting miRNAs have been described in different cancers, including miR-503 in prostate cancer, 59 miR-497 in hepatocellular carcinoma 60 and miR-185 in clear cell renal cell carcinoma. 61 Here we present data indicating that miR-205 targets VEGFA and FGF2 in breast cancer cells leading to decreased activity of PI3K/AKT signaling pathway, increased apoptosis and restoration of drug sensitivity in drug-resistant breast cancer cells.…”

MiR-495 inhibits esophageal squamous cell carcinoma progression by targeting Akt1

“…Deregulation of miRNAs has been reported to both activate and inhibit tumor progression [7]. For example, previous studies have demonstrated the dysregulation of miR-495 in multiple types of cancers, including pancreatic cancer [8], ovarian cancer [9], renal cancer [10], gastric cancer [11], hepatocellular cancer [12], and gallbladder cancer [13]. Furthermore, overexpression of miR-495 inhibits tumor progression by inducing G0/G1 cell cycle arrest [9] and by suppressing angiogenesis and metastasis [12].…”