No abstract

Despite great progress has been made in treatment strategies, colorectal cancer (CRC) remains the predominant life-threatening malignancy with the feature of high morbidity and mortality. It has been widely acknowledged that the dysfunction of immune system, including aberrantly expressed cytokines, is strongly correlated with the pathogenesis and progression of colorectal cancer. As one of the most well-known cytokines that were discovered centuries ago, interleukins are now uncovering new insights into colorectal cancer therapy. Herein, we divide currently known interleukins into 6 families, including IL-1 family, IL-2 family, IL-6 family, IL-8 family, IL-10 family and IL-17 family. In addition, we comprehensively reviewed the oncogenic or antitumour function of each interleukin involved in CRC pathogenesis and progression by elucidating the underlying mechanisms. Furthermore, by providing interleukins-associated clinical trials, we have further driven the profound prospect of interleukins in the treatment of colorectal cancer.

Titanium dioxide nanoparticles (TiO NPs) constitute the top five NPs in use today. In this study, oral administration of 50, 100, and 200 mg/kg body weight (b.w.) TiO NPs increases plasma glucose in mice, whereas 10 and 20 mg/kg b.w. TiO NPs did not. RNA sequencing (RNA-seq) technology was used to investigate genome-wide effects of TiO NPs. Clustering analysis of the RNA-seq data showed the most significantly enriched gene ontology terms and KEGG pathways related to the endoplasmic reticulum (ER) and ER stress. Molecular biology verification showed that 50 mg/kg b.w. and higher doses TiO NPs activated a xenobiotic biodegradation response and increased expression of cytochrome P450 family genes in mouse livers, thus inducing ER stress in mice. ER stress-activated MAPK and NF-κB pathways and induced an inflammation response, resulting in phosphorylation of the insulin receptor substrate 1 and, consequently, insulin resistance. This was the main mechanism by which TiO NPs increased plasma glucose in mice. Meanwhile, ER stress disturbed the monooxygenase system, and thus generated reactive oxygen species (ROS). Relief of ER stress with 4-phenylbutyric acid inhibited all the above effects of TiO NPs, including the generation of ROS. Therefore, TiO NP-induced ER stress was a decisive factor with a central role in plasma glucose disturbance in mice.

BackgroundRecent studies have indicated the possible function of miR-217 in tumorigenesis. However, the roles of miR-217 in colorectal cancer (CRC) are still largely unknown.MethodsWe examined the expression of miR-217 and AEG-1 in 50 CRC tissues and the corresponding noncancerous tissues by qRT-PCR. The clinical significance of miR-217 was analyzed. CRC cell lines with miR-217 upregulation and AEG-1 silencing were established and the effects on tumor growth in vitro and in vivo were assessed. Dual-luciferase reporter gene assays were also performed to investigate the interaction between miR-217 and AEG-1.ResultsOur data demonstrated that miR-217 was significantly downregulated in 50 pairs of colorectal cancer tissues. MiR-217 expression levels were closely correlated with tumor differentiation. Moreover, decreased miR-217 expression was also associated with shorter overall survival of CRC patients. MiR-217 overexpression significantly inhibited proliferation, colony formation and invasiveness of CRC cells by promoting apoptosis and G0/G1 phase arrest. Interestingly, ectopic miR-217 expression decreased AEG-1 expression and repressed luciferase reporter activity associated with the AEG-1 3′-untranslated region (UTR). AEG-1 silencing resulted in similar biological behavior changes to those associated with miR-217 overexpression. Finally, in a nude mouse xenografted tumor model, miR-217 overexpression significantly suppressed CRC cell growth.ConclusionsOur findings suggest that miR-217 has considerable value as a prognostic marker and potential therapeutic target in CRC.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-015-1438-z) contains supplementary material, which is available to authorized users.

y These authors contributed equally to this work.