Liangqing Yao

miR-9 functions as a tumor suppressor in ovarian serous carcinoma by targeting TLN1.

microRNAs (miRNAs) are important regulators of gene expression during tumorigenesis. The downregulation of microRNA-9 (miR-9) has been reported in ovarian serous carcinoma (OSC), indicating a role for miR-9 in this type of cancer. In this study, we investigated the biological significance of miR-9 in OSC in vitro. Using 3 OSC cell lines, SKOV3, CAOV3 and OVCAR3, which underexpresss miR-9, we demonstrate that the exogenous miR-9 transfection inhibits OSC cell proliferation, migration and invasion. In addition, we demonstrate that the focal adhesion protein, talin 1 (TLN1), whose expression has been associated with OSC development and progression to metastasis, is a direct target of miR-9. TLN1 knockdown mimicked the effects of miR-9 overexpression. Moreover, the activation of the TLN1-modulated FAK/AKT pathway was inhibited by the increased miR-9 levels. These results suggest that miR-9 plays a role as a tumor suppressor in OSC by suppressing TLN1 expression.

The proliferation, apoptosis, invasion of endothelial-like epithelial ovarian cancer cells induced by hypoxia

BackgroundEpithelial ovarian cancer is one of the most malignant cancers in women because metastasis occurs in the most of patients by the time of diagnosis. Cancer cells have strong capacity to form angiogenesis or vasculogenic mimicry, which plays the major role in its malignant phenotype. Vasculogenic mimicry might contribute to the failure of the angiogenesis-targeted therapy strategies. Under the microenvironment of the tumor, hypoxia is the most common phenomena because of the vast energy and oxygen consuming. In the present study, the endothelial-like cells induced by hypoxia from SKOV-3 and ES-2 ovarian cancer cells were harvested to investigate the changes in their biological behaviors.MethodsThe endothelial-like cells from SKOV-3 and ES-2 cells were harvested by laser capture microdissection. The biological behaviors of the endothelial-like cells, including proliferation, cell cycle, apoptosis, invasion and telomerase activity were determined by MTT, FCM, Transwell chamber and TRAP-ELISA methods. HIF-1α is the most important factor for the behavior changes under hypoxic condition. Some other genes relative to biological behaviors are also changes following the changes of HIF-1α. In order to elucidate the underlying mechanisms for these changes by hypoxia, the relative genes expressions including HIF-1α, CyclinD1, Flk-1, VEGF, p53 and V-src were determined by real-time PCR.ResultsSKOV-3 and ES-2 cells were resistant to hypoxia by adoption of proliferation, apoptosis, differentiation and invasion. Combined with other studies, the more poorly cancer cells differentiate, the more strongly cells are resistant to hypoxia, the more possible to form vasculogenic mimicry. The changes in the expression of HIF-1α, and HIF-1α-dependent VEGF, Flk-1, Cyclin D1, and HIF-1α-independent p53 have been involved in this process.ConclusionsHIF-1α took an important role in the behavioral changes of SKOV-3 and ES-2 cells by hypoxia. At the same time, other mechanisms were also involved in this process.

Constructing predictive models for vaginal surgery in patients with noninvasive gynecological conditions

To develop predictive models for vaginal operative route selection based on clinical variables that can be easily assessed preoperatively in patients with noninvasive gynecological conditions.

Predicting the success of vaginal surgery: a quantitative risk assessment model for future investigation

OBJECTIVEnTo introduce a model incorporating expected risks for a vaginal procedure based on objective measurements of a patients characteristics and propose it as a potential tool to assist in the selection of candidates for vaginal surgery.nnnSTUDY DESIGNnA quantitative model consisting of 13 clinical variables identified as risk factors in a prospective vaginal procedure was developed. Medical records of 315 women undergoing a set of routine gynecological surgeries via the vaginal, laparoscopic, and abdominal routes were obtained during January 2010 and November 2011. These surgeries included hysterectomy, myomectomy, bilateral or unilateral salpingo-oophorectomy and adnexal cystectomy. After that, each patient was scored according to the model. Sensitivity and specificity of the model were analyzed in one data set (cohort I) by receiver operating characteristic (ROC) curve and independently validated in a second data set (cohort II).nnnRESULTSn175 patients were included in cohort I while the other 140 patients formed cohort II. The intra- and post-operative complication rates were 0.6% and 0%, respectively. A vaginal procedure was predicted with good accuracy (AUC=0.852). The sensitivity was 86.0% and specificity was 72.0% at an optimal cut-off point of score=3. The predication accuracy of this model was further validated in cohort II and reached as high as 85.7%. Furthermore, the score was significantly associated with the volume of estimated blood loss and the duration of operation time (P<0.05).nnnCONCLUSIONnOur quantitative risk assessment model predicts safe vaginal surgery with good accuracy. Predictive tools based on such a model could help surgeons to optimize patient selection and thus contribute to reducing costs while enhancing patients satisfaction. We invite other researchers to modify and validate the model in other populations.

Human mesenchymal stem cells in the tumour microenvironment promote ovarian cancer progression: the role of platelet-activating factor

BackgroundThe tumour microenvironment conferred by mesenchymal stem cells (MSCs) plays a key role in tumour development and progression. We previously determined that platelet-activating factor receptor (PAFR) was overexpressed in ovarian cancer cells (OCCs) and that PAF can promote ovarian cancer progression via PAF/PAFR-mediated inflammatory signalling pathways. Evidence suggests that MSCs can secrete high concentrations of PAF. Here, we investigated the role of PAF/PAFR signalling in the microenvironment mediated by MSCs and OCCs and its effect on cancer progression.MethodsThe PAF concentrations in the culture media of MSCs, OCCs and co-cultured MSCs and OCCs were determined by ELISA. The effects of MSCs on OCCs in vitro were assessed on cells treated with conditioned medium (CM). The expression and phosphorylation of key proteins in the PAF/PAFR signalling pathway were evaluated. In vivo, MSCs/RFP and SKOV3 cells were co-administered at different proportions to nude mice by interscapular injection. Mice in the WEB2086 group were intraperitoneally injected with the PAFR antagonist WEB2086 at a dose of 1xa0mg/kg.d for the duration of the animal experiments. Tumour progression was observed, and the weight and survival time of mice were measured. The PAF concentration in peripheral and tumour site blood was determined by ELISA.ResultsHigh concentrations of PAF were detected in CM from MSCs and MSCs co-cultured with OCCs. Both types of medium promoted non-mucinous OCC proliferation and migration but had no effect on mucinous-type OCCs. These effects could be blocked by PAFR inhibitors. The expression and phosphorylation of key proteins in the PAF/PAFR pathway significantly increased upon treatment with PAF and MSC-CM. In vivo, the tumour volume was larger following co-injection of SKOV3 cells and MSCs/RFP than following injection of SKOV3 cells alone. The tumour-promoting effect of MSCs/RFP was blocked by the PAFR antagonist WEB2086. Serum PAF concentrations significantly increased in co-injected mice.ConclusionOur results suggest that the tumour-promoting effect of MSCs on OCCs via their cross-talk in the tumour microenvironment was, at least in part, mediated by the PAF/PAFR pathway, suggesting a new target for the treatment of ovarian cancer.