Exosome-derived SNHG16 sponging miR-4500 activates HUVEC angiogenesis by targeting GALNT1 via PI3K/Akt/mTOR pathway in hepatocellular carcinoma

Accumulating evidence suggests cancer-derived exosomes play an important role in promoting angiogenesis. Long noncoding RNA small nucleolar RNA host gene 16 (SNHG16) is known to aggravate hepatocellular carcinoma (HCC) progression. However, the function of exosomal SNHG16 in HCC angiogenesis remains unclear. In this study, the expression of SNHG16 was significantly upregulated in HCC tissues and cell lines. The proliferative, migratory, and angiogenic abilities of HUVECs were enhanced after exposure to exosomes derived from HCC cells by transmitting SNHG16. In addition, SNHG16 was validated to promote the biological function of HUVECs directly. Exosomal SNHG16 increased GALNT1 expression to promote angiogenesis via sponging miR-4500. SNHG16/miR-4500/GALNT1 axis played an important role in exosome-mediated angiogenesis and tumor growth in vitro and vivo. Furthermore, SNHG16 activated PI3K/Akt/mTOR pathway via competing endogenous miR-4500 and GALNT1. Meanwhile, the expression of plasma exosomal SNHG16 upregulated in the plasma of HCC patients. These data elucidated the essential role of exosomal SNHG16 in communication between HCC cells and endothelial cells. Exosomal SNHG16 could be utilized as a therapeutic target for anti-angiogenesis in HCC progression.

Automated summary

The study revealed that SNHG16, through exosomes, enhances the proliferative, migratory, and angiogenic effects of HCC cells on endothelial cells, further activating the PI3K/Akt/mTOR pathway to promote tumor growth. Exosomal SNHG16 may serve as a therapeutic target for anti-angiogenesis in HCC progression.