Autophagy is an evolutionarily conserved lysosome-dependent catabolic process which degrades cell’s components in order to recycle substrates to exert optimally and adapt to tough circumstances. It is a critical cellular homeostatic mechanism with stress resistance, immunity, antiaging, and pro-tumor or anti-tumor effects. Among these, the role of autophagy in cancer is the most eye-catching that is not immutable but dynamic and highly complex. Basal autophagy acts as a tumor suppressor by maintaining genomic stability in normal cells. However, once a tumor is established, unbalanced autophagy will contribute to carcinoma cell survival under tumor microenvironment and in turn promote tumor growth and development. The dynamic role of autophagy can also apply on hepatocellular carcinoma (HCC). HCC is a highly malignant cancer with high morbidity and poor survival rate. Decline or overexpression of autophagic essential genes such as ATG7, ATG5 or Beclin 1 plays a key role in the occurrence and development of HCC but the exact mechanisms are still highly controversial. Signaling pathways or molecules involving in autophagy, for example PI3K/AKT/mTOR pathway, ERK/MAPK pathway, PERK pathway, p53, LncRNA PTENP1 (Long non-coding RNA PTENP1), microRNA-375 and so on, occupy an important position in the complex role of autophagy in HCC. Here, we discuss the dynamic role, the signaling pathways and the potential prognostic and therapy value of autophagy in HCC.

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.

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