The Role And Its Mechanism Of YB-1on Cervical Cancer EMT Induced By Hypoxic Microenvironment

[Objective]Investigate the role and its mechanism of YB-1on cervical cancer EMT in hypoxia microenvironment, to provide an experimental basis of the targeted therapy for cervical cancer.[methods](1) The expression of YB-1and Vimentin in middle and advanced stage cervical cancer tissue microarray chip which contains78cases were evaluated by Streptomyces avidin peroxidase(S-P)-immunohistochemistry method to explore their relationship with clinical pathological characteristics and the correlation among them.(2) The Hela cells were treated with Cobalt chloride(CoCl2) to mimic the hypoxia microenvironment, the concentration and treatment duration of CoCl2were optimized by MTT method, which was used to detect the cell proliferation vitality.After6h treated with CoCl2, The morphologies of the Hela cells were studied by invert microscope and the expression of YB-1, MMP-2and Vimentin proteins in cells were measured by Immunofluorescence.[results](1) The expression of YB-1in78cases of cervical cancer tissue was30.8%(24/78). The expression of YB-1protein were not associated with age(P=0.477),tumor histology type(P=0.962) and lymph node metastasis(P=0.224); but significantly related to FIGO stage and differentiation degree respectively(P<0.05). The expression of YB-1in IV stage were significantly higher to Ⅱ and Ⅲ stage(P=0.003). The expressions of YB-1were22.2%(4/18),33.3%(17/51) and37.5%(3/8) in well, moderate and poor differentiation cervical cancer tissues respectively. The expressions of YB-1in cervical cancer increased with the differentiation degree decreased(P=0.001). The expression of Vimentin in78cases of cervical cancer tissue was38.5%(30/78). The expression of Vimentin protein was not associated with age(P=0.616), but significantly related to the tumor histology type(P=0.046), lymph node metastasis(P=0.004), FIGO stage (P=0.020) and differentiation degree respectively(P=0.000). With the increase of FIGO stage and the emergence of lymph node metastasis, the expression of Vimentin increased gradually (P<0.05). The expression of YB-1was positive Correlation with Vimentin expression in cervical cancer(r=0.375,P<0.01).(2) The Hela cells vitality was significantly inhibit by CoCl2concentration-time dependent. The optimal CoCl2concentration was150μmol/L and the optimum treatment time was six hours (P<0.05).(3) Under the hypoxia condition, the Hela cells obtained the morphological characteristics of stromal cells gradually. Hela cells were found gradually stretch, deformation, widened intercellular gap and narrow protuberance by inverted microscope observation after6h treated with150μmol/LCoCl2.(4) The expression of YB-1, MMP-2and Vimentin of Hela cells in hypoxia microenvironment were significantly higher than those in the ordinary oxygen cells group (P<0.05), and there were significant positive Correlations among them (P<0.05).[conclusions]YB-1may play a key role on cervical cancer EMT in hypoxia microenvironment through YB-1-MMP-2-Vimentin pathway by up-regulation Vimentin expression.