Cisplatin is commonly used in ovarian cancer chemotherapy, however, chemoresistance to cisplatin remains a great clinical challenge. Oncogenic transcriptional factor FOXM1 has been reported to be overexpressed in ovarian cancer. In this study, we aimed to investigate the potential role of FOXM1 in ovarian cancers with chemoresistance to cisplatin. Our results indicate that FOXM1 is upregulated in chemoresistant ovarian cancer samples, and defends ovarian cancer cells against cytotoxicity of cisplatin. FOXM1 facilitates DNA repair through regulating direct transcriptional target EXO1 to protect ovarian cancer cells from cisplatin-mediated apoptosis. Attenuating FOXM1 and EXO1 expression by small interfering RNA, augments the chemotherapy efficacy against ovarian cancer. Our findings indicate that targeting FOXM1 and its target gene EXO1 could improve cisplatin effect in ovarian cancer, confirming their role in modulating cisplatin sensitivity.

Citrate synthase (CS), one of the key enzymes in the tricarboxylic acid (TCA) cycle, catalyzes the reaction between oxaloacetic acid and acetyl coenzyme A to generate citrate. Increased CS has been observed in pancreatic cancer. In this study, we found higher CS expression in malignant ovarian tumors and ovarian cancer cell lines compared to benign ovarian tumors and normal human ovarian surface epithelium, respectively. CS knockdown by RNAi could result in the reduction of cell proliferation, and inhibition of invasion and migration of ovarian cancer cells in vitro. The drug resistance was also inhibited possibly through an excision repair cross complementing 1 (ERCC1)-dependent mechanism. Finally, upon CS knockdown we observed significant increase expression of multiple genes, including ISG15, IRF7, CASP7, and DDX58 in SKOV3 and A2780 cells by microarray analysis and real-time PCR. Taken together, these results suggested that CS might represent a potential therapeutic target for ovarian carcinoma.

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By using multisourced data and two sets of sensitivity runs from the coupled general circulation model CESM1.2.0, we investigated the effects of the spring [March, April, and May (MAM)] surface sensible heating over the Tibetan Plateau (SHTP) on the interannual variability of the North Pacific Ocean sea surface temperature (SST) and mixed layer. The results indicated that an above-normal MAM SHTP can generate a Rossby wave downstream and form an anomalous equivalent barotropic anticyclone over the North Pacific, inducing anticyclonic wind stress anomalies. As a result of Ekman transport and Ekman pumping, sea currents converge near 40°N, accompanied by weak downwelling motion. The mixed layer heat budget diagnosis indicates that the net heat fluxes, together with meridional advection anomalies, contributed significantly to changes in the mixed layer temperature (MLT). As a result, the SST anomalies (SSTAs) and MLT anomalies both present a horseshoelike pattern. In addition, the significant warm SSTAs show a maximum in the late spring, but the significant warm MLT anomalies centered under the sea surface (25-m depth) could be sustained until summer, acting like a signal storage for the anomalous spring SHTP. Moreover, the midlatitude ocean–atmosphere interaction provides a positive feedback on the development of the anomalous anticyclone over the North Pacific, since the SSTA pattern could strengthen the oceanic front and induce more active transient eddy activities. The eddy vorticity forcing that is dominant among the total atmospheric forcings tends to produce an equivalent barotropic atmospheric high pressure, which in turn intensifies the initial anomalous anticyclone.