AQP9 suppresses hepatocellular carcinoma cell invasion through inhibition of hypoxia‐inducible factor 1α expression under hypoxia

Abstract Background and Aim Intratumor hypoxia is a hallmark of hepatocellular carcinoma (HCC) and is associated with an aggressive tumor phenotype. Although it has been shown that AQP9 plays an important role in HCC, the relevance between hypoxia and AQP9 is still unknown. Methods We established in vitro normoxic or hypoxic models to investigate the role of AQP9 in the regulation of hypoxia‐inducible factor 1α (HIF‐1α) and hypoxia‐enhanced invasion of hepatoma cells. Molecular expression was detected using western blot or quantitative polymerase chain reaction. Cell invasion ability was determined using Transwell invasion assay. In vivo xenograft experiment was used to detect the role of AQP9 on tumor growth. Results Our present study revealed a decrease in the expression levels of AQP9 in hypoxic microenvironments. Overexpression of AQP9 led to a decreased expression of HIF‐1α; conversely, suppression of AQP9 in HCC cells had an opposite effect. Furthermore, up‐regulated AQP9 blocked the hypoxic‐enhanced invasion of HCC cells. The overexpression of AQP9 inhibited the growth of tumors and HIF‐1α expression in vivo . Conclusions These data suggest that AQP9 acts as a tumor suppressor in HCC invasion via the regulation of HIF‐1α expression in the tumor hypoxic microenvironment.