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AQP3

BACKGROUND: Gastric carcinoma (GC) is a common and lethal malignancy, and epithelial-mesenchymal transition (EMT) is believed to contribute to invasive and metastatic tumor growth. Aquaporin 3 (AQP3) is overexpressed in human GC tissues, while human epidermal growth factor (EGF) and hepatocyte growth factor, which can induce EMT, are able to up-regulate AQP3 expression, subsequently promoting GC cell migration and proliferation. The purpose of this study was to investigate the effects of AQP3 on EMT in human GC. METHODS: AQP3 and EMT-related proteins were detected by immunohistochemistry in human GC specimens and their clinical significance evaluated. AQP3 knockdown was attempted using small interfering RNAs, while EGF was used to up-regulate AQP3 expression. Western blotting, real-time quantitative polymerase chain reaction assays and immunofluorescence were used to evaluate changes in expression of AQP3 and EMT-related proteins in the SGC7901 and MGC803 human GC cell lines. RESULTS: AQP3 up-expression was associated with EMT-related proteins in human GC specimens, which correlated with poor prognosis for GC. AQP3 modulated GC cell proliferation, migration and invasion in vitro, and induced E-cadherin repression. AQP3 also up-regulated the expression of vimentin and fibronectin in vitro. The PI3K/AKT/SNAIL signaling pathway was likely involved in the induction of EMT by AQP3 in GC. CONCLUSIONS: AQP3 promotes EMT in human cases of GC, allowing us to understand the mechanisms of AQP3 in GC progression, thus providing a potential strategy for its treatment.

It has been reported that aquaporin 3 (AQP3) expression is associated with the progression of numerous types of cancer and microRNA (miRNA/miR) processing. However, the effects and precise mechanisms of AQP3 in osteosarcoma (OS) have not been fully elucidated. The present study aimed to investigate the interaction between AQP3 and miR488 in OS. The reverse transcriptionquantitative polymerase chain reaction (RTqPCR) assay was performed to detect the levels of AQP3 and miR488 in OS tissues and cell lines, respectively. Cell proliferation, invasion and epithelial-mesenchymal transition (EMT) were detected to analyze the biological functions of miR488 and AQP3 in OS cells. Furthermore, mRNA and protein levels of AQP3 was measured by RTqPCR and western blot analysis. Furthermore, AQP3 was validated as an miR488 target using luciferase assays in OS cells. The present study revealed that the miR488 level was significantly downregulated in OS tissues and cell lines, and that the expression of AQP3 was markedly increased. Notable, the low miR488 expression level was associated with upregulated AQP3 expression in OS tissues. Furthermore, introduction of miR488 markedly suppressed the proliferation, invasion and EMT of OS cells. However, miR488-knockdown increased the proliferation, invasion and EMT of OS cells. The present study demonstrated that miR488 could directly target AQP3 using bioinformatics analysis and luciferase reporter assays. In addition, AQP3-silencing had similar effects to miR488 overexpression on OS cells. Overexpression of AQP3 in OS cells partially reversed the inhibitory effects of miR488 mimic. miR488 inhibited the proliferation, invasion and EMT of OS cells by directly downregulating AQP3 expression, and miR488 targeting AQP3 was responsible for inhibition of the proliferation, invasion and EMT of OS cells.