Tetraspanin 1 promotes epithelial-to-mesenchymal transition and metastasis of cholangiocarcinoma via PI3K/AKT signaling.

BACKGROUND:Numerous studies have demonstrated that tetraspanin 1 a transmembrane protein, functions as an oncoprotein in many cancer types. However, its role and underlying molecular mechanism in cholangiocarcinoma (CCA) progression remain unclear. METHODS:In the present study, the expression of in human CCA and adjacent nontumor tissues was examined using real-time PCR, western blot and immunohistochemistry. The effect of Tduanyu1842N1 on proliferation and metastasis was evaluated by functional assays both in vitro and in vivo. A luciferase reporter assay was performed to investigate the interaction between microRNA-194-5p (miR-194-5p) and Tduanyu1842N1 3'-untranslated region. Co-immunoprecipitation (co-IP) was used to confirm the interaction between Tduanyu1842N1 protein and integrin α6β1 and western blot was used to explore Tduanyu1842N1 mechanism. RESULTS:We found that Tduanyu1842N1 was frequently upregulated in CCA and high levels of Tduanyu1842N1 correlated with TNM stage, especially metastasis in CCA. Tduanyu1842N1 overexpression promoted CCA growth, metastasis, and induced epithelial-to-mesenchymal transition (EMT), while its silencing had the opposite effect both in vitro and in vivo. To explore the differential expression of we screened miR-194-5p as the upstream regulator of A combination of high-level Tduanyu1842N1 and low-level miR-194-5p predicted poor prognosis in patients with CCA. Furthermore, in accordance with the functional characteristics of the superfamily, we proved that Tduanyu1842N1 interacted with integrin α6β1 to amplify the phosphoinositide-3-kinase (PI3K)/AKT/glycogen synthase kinase (GSK)-3β/Snail family transcriptional repressor (Snail)/phosphatase and tensin homolog (PTEN) feedback loop. CONCLUSION:The results indicate that Tduanyu1842N1 could be a potential therapeutic target for CCA.

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