Introduction In this study, we report on the development of an effective delivery system for siRNAs; a novel cell-penetrating peptide (CPP), T9(dR), obtained from transportan (TP), was used for in vivo and in vitro testing. Methods In this study, toxicity of T9(dR) and TP and efficient delivery of siRNA were tested in 293T, MDCK, RAW, and A549 cells. Furthermore, T9(dR)- and TP-delivered siRNAs against nucleoprotein (NP) gene segment of influenza virus (siNP) were studied in both cell lines and mice. Results Gel retardation showed that T9(dR) effectively condensed siRNA into nanoparticles sized between 350 and 550 nm when the mole ratio of T9(dR) to siRNA was ≥4:1. In vitro studies demonstrated that T9(dR) successfully delivered siRNA with low cellular toxicity into several cell lines. It was also observed that T9(dR)-delivered siRNAs inhibited replication of influenza virus more efficiently as compared to that delivered by TP into the MDCK and A549 cells. It was also noticed that when given a combined tail vein injection of siNP and T9(dR) or TP, all mice in the 50 nmol siNP group infected with PR8 influenza virus survived and showed weight recovery at 2 weeks post-infection. Conclusion This study indicates that T9(dR) is a promising siRNA delivery tool with potential application for nucleotide drug delivery.

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The X-ray repair cross-complementing group 3 (XRCC3), one of the DNA repair genes, was suggested to play an imperative role in the development of carcinogenesis. The objective of this study was to evaluate the role of the XRCC3 T241M polymorphism in bladder cancer susceptibility in a Chinese population. We genotyped 150 bladder cancer cases and 150 healthy controls who had been frequency matched to cases by age and sex. Genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism analysis. A significant association was found between smoker and bladder cancer [odds ratio (OR)=1.97, 95% confidence interval (CI)=1.24-3.13, p=0.004]. The XRCC3 241MM genotype was more frequent in the bladder cancer group than in the healthy controls group (OR=3.22, 95% CI=1.14-9.11, p=0.03). There were no significant associations between any genotypes and the stage, grade, and histological type of bladder cancer. Our study suggested an increased risk role of XRCC3 241MM genotype in bladder cancer susceptibility in a Chinese population.

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Aberrant glucose metabolism is a characteristic of bladder cancer. Hyperglycemia contributes to the development and progression of bladder cancer. However, the underlying mechanism by which hyperglycemia promotes the aggressiveness of cancers, especially bladder cancer, is still incompletely understood. N6-methyladenosine (m6A) modification is a kind of methylation modification occurring at the N6 position of adenosine that is important for the pathogenesis of urological tumors. Recently, it was found that the m6A reader YTHDC1 is regulated by high-glucose conditions. In our study, we revealed that YTHDC1 is not only regulated by high-glucose conditions but is also downregulated in bladder cancer tissue and associated with the prognosis of cancer. We also showed that YTHDC1 suppresses the malignant progression of and the glycolytic process in bladder cancer cells in an m6A-dependent manner and determined that this effect is partially mediated by GLUT3. Moreover, GLUT3 was found to destabilize YTHDC1 by upregulating RNF183 expression. In summary, we identified a novel YTHDC1/GLUT3/RNF183 feedback loop that regulates disease progression and glucose metabolism in bladder cancer. Collectively, this study provides new insight regarding the pathogenesis of bladder cancer under hyperglycemic conditions and might reveal ideal candidates for the development of drugs for bladder cancer.