Abstract
The epithelial-mesenchymal transition (EMT) is one of the crucial procedures for cancer invasion and distal metastasis. Despite undergoing intensive studies, the mechanisms underlying EMT remain to be completely elucidated. Here, we identified that apoptosis-stimulating protein of p53-2 (ASPP2) is a novel target of MiR-205 in various cancers. Interestingly, the binding site of MiR-205 at the 3'-untranslated region of ASPP2 was highly conserved among different species. An inverse correlation between MiR-205 and ASPP2 was further observed in vivo in cervical cancers, suggesting MiR-205 may be an important physiological inhibitor of ASPP2. Hypoxia is a hallmark of solid tumor microenvironment and one of such conditions to induce EMT. Notably, MiR-205 was remarkably induced by hypoxia in cervical and lung cancer cells. A marked suppression of ASPP2 was observed simultaneously. Further studies confirmed that hypoxia-induced ASPP2 suppression was mainly attributed to the elevated MiR-205. Interestingly, the alteration of MiR-205/ASPP2 under hypoxia was accompanied with the decreased epithelial marker E-cadherin and increased mesenchymal marker Vimentin, as well as a morphological transition from the typical cobblestone-like appearance to the mesenchymal-like structure. More importantly, MiR-205 mimics or ASPP2 silencing similarly promoted EMT process. By contrast, ASPP2 recovery or MiR-205 inhibitor reversed MiR-205-dependent EMT. Further studies demonstrated that the newly revealed MiR-205/ASPP2 axis promoted cell migration and also increased cell proliferation both in vivo and in vitro. These data together implicated a critical impact of MiR-205/ASPP2 on promoting EMT. MiR-205/ASPP2 may be potential diagnostic and therapeutic biomarkers in cervical and lung cancers.