Increased miR‐222 levels are associated with a poor prognosis in patients with bladder cancer. However, the role of miR‐222 remains unclear. In the present study, we found that miR‐222 enhanced the proliferation of both the T24 and the 5637 bladder cancer cell lines. Overexpression of miR‐222 attenuated cisplatin‐induced cell death in bladder cancer cells. miR‐222 activated the Akt/mTOR pathway and inhibited cisplatin‐induced autophagy in bladder cancer cells by directly targeting protein phosphatase 2A subunit B (PPP2R2A). Blocking the activation of Akt with LY294002 or mTOR with rapamycin significantly prevented miR‐222‐induced proliferation and restored the sensitivity of bladder cancer cells to cisplatin. These findings demonstrate that miR‐222 modulates the PPP2R2A/Akt/mTOR axis and thus plays a critical role in regulating proliferation and chemotherapeutic drug resistance. Therefore, miR‐222 may be a novel therapeutic target for bladder cancer.

Background: Genomic DNA methylation plays an important role in both the occurrence and development of bladder cancer. Kaempferol (Kae), a natural flavonoid that is present in many fruits and vegetables, exhibits potent anti-cancer effects in bladder cancer. Similar to other flavonoids, Kae possesses a flavan nucleus in its structure. This structure was reported to inhibit DNA methylation by suppressing DNA methyltransferases (DNMTs). However, whether Kae can inhibit DNA methylation remains unclear. Methods: Nude mice bearing bladder cancer were treated with Kae for 31 days. The genomic DNA was extracted from xenografts and the methylation changes was determined using an Illumina Infinium HumanMethylation 450 BeadChip Array. The ubiquitination was detected using immuno-precipitation assay. Results: Our data indicated that Kae modulated DNA methylation in bladder cancer, inducing 103 differential DNA methylation positions (dDMPs) associated with genes (50 hyper-methylated and 53 hypo-methylated). DNA methylation is mostly relied on the levels of DNMTs. We observed that Kae specifically inhibited the protein levels of DNMT3B without altering the expression of DNMT1 or DNMT3A. However, Kae did not downregulate the transcription of DNMT3B. Interestingly, we observed that Kae induced a premature degradation of DNMT3B by inhibiting protein synthesis with cycloheximide (CHX). By blocking proteasome with MG132, we observed that Kae induced an increased ubiquitination of DNMT3B. These results suggested that Kae could induce the degradation of DNMT3B through ubiquitin-proteasome pathway. Conclusion: Our data indicated that Kae is a novel DNMT3B inhibitor, which may promote the degradation of DNMT3B in bladder cancer.

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This paper mainly studies the heat transfer performance of backplane micro-channel heat pipes by establishing a steady-state numerical model. Compared with the experimental data, the heat transfer characteristics under different structure parameters and operating parameters were studied, and the change of heat transfer coefficient inside the system, the air outlet temperature of the back plate and the influence of different environmental factors on the heat transfer performance of the system were analyzed. The results show that the overall error between simulation results and experimental data is less than 10%. In the range of the optimal filling rate (FR = 64.40%–73.60%), the outlet temperature at the lowest point and the highest point of the evaporation section is 22.46 °C and 19.60 °C, the temperature difference does not exceed 3 °C, and the distribution gradient in vertical height is small and the air outlet temperature is uniform. The heat transfer coefficient between the evaporator and the condenser is larger than the heat transfer coefficient under the conditions of low and high liquid charge rate. It increases gradually along the flow direction, and decreases gradually with the flow rate of the condenser. When the width of the flat tube of the evaporator increases from 20 mm to 28 mm, the internal pressure drop of the evaporator decreases by 45.83% and the heat exchange increases by 18.34%. When the number of evaporator slices increases from 16 to 24, the heat transfer increases first and then decreases, with an overall decrease of 2.86% and an increase of 87.67% in the internal pressure drop of the evaporator. The inclination angle of the corrugation changes from 30° to 60°, and the heat transfer capacity and pressure drop increase. After the inclination angle is greater than 60°, the heat transfer capacity and resistance decrease. The results are of great significance to system optimization design and engineering practical application.