Background/Aims: MicroRNA-218 (miR-218) is down-regulated in many malignancies that have been implicated in the regulation of diverse processes in cancer cells. However, the involvement of miR-218 in chemo-sensitivity to cisplatin and the precise mechanism of this action remained unknown in bladder cancer. Methods: qRT-PCR was used to detect miR-218 and its target Glut1 expression in bladder cancer cell lines T24 and EJ. CCK-8 method was utilized to measure the cell viability. IC 50 was calculated via a probit regression model. Glut1 was detected by western blotting for analysis of potential mechanism. Luciferase reporter assay was utilized to validate Glut1 as a direct target gene of miR-218. The intracellular level of GSH and ROS were determined using a commercial colorimetric assay kit and 2’, 7’-dichlorodihydro-fluorescein diacetate, respectively. Results: Over-expression of miR-218 significantly reduced the rate of glucose uptake and total level of GSH and enhanced the chemo-sensitivity of bladder cancer to cisplatin. Mechanistically, Glut1 was found to be a direct and functional target of miR-218. Up-regulation of Glut1 could restore chemo-resistance in T24 and EJ cells. On the contrary, knockdown of Glut1 could generate a similar effect as up-regulating the expression of miR-218. Conclusions: MiR-218 increases the sensitivity of bladder cancer to cisplatin by targeting Glut1. Restoration of miR-218 and repression of glut1 may provide a potential strategy to restore chemo-sensitivity in bladder cancer.
It has been reported that Annexin A2 (ANXA2) is up-regulated in hepatocellular carcinoma (HCC), but the roles of ANXA2 in the migration and invasion of HCC cells have not been determined. In this study, we found that ANXA2-specific siRNA (si-ANXA2) significantly inhibited the migration and invasion of HCC cells co-cultured with fibroblasts in vitro. In addition, the production of MMP-2 by fibroblasts cultured in supernatant collected from si-ANXA2-transfected HCC cells was notably down-regulated. ANXA2 was also found to be co-localized and co-immunoprecipitated with CD147. Further investigation revealed that the expression of ANXA2 in HCC cells affected the shedding of CD147-harboring membrane microvesicles, acting as a vehicle for CD147 in tumor-stromal interactions and thereby regulating the production of MMP-2 by fibroblasts. Together, these results suggest that ANXA2 enhances the migration and invasion potential of HCC cells in vitro by regulating the trafficking of CD147-harboring membrane microvesicles.
Introduction: Assessment of lymph node metastasis (LNM) is crucial for treatment decision and prognosis prediction for endometrial cancer (EC). However, the sensitivity of the routinely used magnetic resonance imaging (MRI) is low in assessing normal-sized LNM (diameter, 0–0.8 cm). We aimed to develop a predictive model based on magnetic resonance (MR) images and clinical parameters to predict LNM in normal-sized lymph nodes (LNs).Materials and Methods: A total of 200 retrospective patients were enrolled and divided into a training cohort (n = 140) and a test cohort (n = 60). All patients underwent preoperative MRI and had pathological result of LNM status. In total, 4,179 radiomic features were extracted. Four models including a clinical model, a radiomic model, and two combined models were built. Area under the receiver operating characteristic (ROC) curves (AUC) and calibration curves were used to assess these models. Subgroup analysis was performed according to LN size. All patients underwent surgical staging and had pathological results.Results: All of the four models showed predictive ability in LNM. One of the combined models, ModelCR1, consisting of radiomic features, LN size, and cancer antigen 125, showed the best discrimination ability on the training cohort [AUC, 0.892; 95% confidence interval [CI], 0.834–0.951] and test cohort (AUC, 0.883; 95% CI, 0.786–0.980). The subgroup analysis showed that this model also indicated good predictive ability in normal-sized LNs (0.3–0.8 cm group, accuracy = 0.846; <0.3 cm group, accuracy = 0.849). Furthermore, compared with the routinely preoperative MR report, the sensitivity and accuracy of this model had a great improvement.Conclusions: A predictive model was proposed based on MR radiomic features and clinical parameters for LNM in EC. The model had a good discrimination ability, especially for normal-sized LNs.
Prevotella intermedia, a major periodontal pathogen, plays important roles in the initiation and development of periodontitis by stimulating the release of proinflammatory cytokines, proteinases and matrix metalloproteinases (MMPs). Our previous study demonstrated that P. intermedia induced MMP-9 expression in human periodontal ligament (hPDL) cells. In this study, we examined the effects of P. intermedia on other MMPs' expression. Semi-quantitative reverse transcriptase (RT)-PCR analysis revealed that P. intermedia ATCC 25611 supernatant increased MMP-1 and MMP-8 mRNA expression in a concentration- and time-dependent manner. Enzyme-linked immunosorbent assay and Western blot results confirmed the RT-PCR results at the protein level. Cyclooxygenase inhibitor indomethacin significantly attenuated the upregulatory effects of P. intermedia on MMP-1 and MMP-8 expression. Extracellular signal-related kinase inhibitor PD98059 and c-Jun N-terminal kinase inhibitor SP600125 considerably decreased the upregulated level of MMP-1, whereas p38 inhibitor SB203580 markedly inhibited MMP-8 expression, suggesting that prostaglandin E(2) and mitogen-activated protein kinase signaling pathways are involved in P. intermedia-induced MMP-1 and MMP-8 upregulation. Our results indicate that P. intermedia might contribute to periodontal connective tissue and bone matrix destruction through upregulating MMP production.
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