AP-2? inhibits hepatocellular carcinoma invasion and metastasis through Slug and Snail to suppress epithelial-mesenchymal transition.
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ABSTRACT: Transcription factor AP-2? plays an important role in human cancer, but its clinical significance in hepatocellular carcinogenesis is largely unknown. Methods: AP-2? expression was detected in human hepatocellular cancer (HCC) tissues and cell lines. The effects of AP-2? on HCC proliferation, migration, invasion, tumor formation and metastasis were evaluated by MTT, colony formation and transwell assays in vitro and mouse experiments in vivo. The association between AP-2? and miR-27a/EMT markers in HCC cell lines and tissues was analyzed. Results: AP-2? expression was decreased in HCC tissues and cell lines. Reduced expression of AP-2? was significantly associated with more advanced tumor stages and larger tumor sizes. The overexpression of AP-2? reduced HCC proliferation, migration, invasion, tumor formation and metastasis in vitro and in vivo. Additionally, AP-2? overexpression increased the sensitivity of HCC cells to cisplatin. Moreover, AP-2? modulates the levels of EMT markers through Slug and Snail in HCC cell lines and tissues. Furthermore, oncogenic miR-27a inhibits AP-2? expression by binding to the AP-2? 3' untranslated region (UTR) and reverses the tumor suppressive role of AP-2?. Conclusion: These results suggested that AP-2? is lowly expressed in HCC by inhibiting EMT signaling to regulate HCC cell growth and migration. Therefore, AP-2? in the novel miR-27a/AP-2?/Slug/EMT regulatory axis enhances the chemotherapeutic drug sensitivity of HCC and might represent a potential target for evaluating the treatment and prognosis of human HCC.
SUBMITTER: Yang L
PROVIDER: S-EPMC6037033 | biostudies-literature | 2018
REPOSITORIES: biostudies-literature
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