Recent studies have shown that competing endogenous RNAs (ceRNAs) play an important role in the regulation of gene expression, and participate in a wide range of biological processes, including carcinogenesis. Long non-coding RNA PTENP1, the pseudogene of PTEN tumor suppressor, has been reported to exert its tumor suppressive function via modulation of PTEN expression in many malignancies. However, whether a PTENP1∼miRNA∼PTEN ceRNA network exists and how it functions in gastric cancer (GC) remains elusive. In order to identify and characterize the PTENP1∼miRNA∼PTEN ceRNA network in GC, we first determined PTENP1 levels in clinical GC samples and found that PTENP1 and PTEN were concurrently downregulated in these samples. We further demonstrated that PTENP1 could act as a ceRNA to sponge miR-106b and miR-93 from targeting PTEN for downregulation using a novel ceRNA in vitro gradient assay. Thus, we revealed a tumor suppressive role of PTENP1 as ceRNA in GC and pinpointed the specific miRNAs decoyed by PTENP1, highlighting the emerging roles of ceRNAs in the biological regulation of GC cells and their possible clinical significance.

ObjectiveConcentrating on oncogenic role and increased plasma expression of microRNA(miR) 106b~25 clusters (involving miR 106b, miR 93 and miR 25), we evaluated significance of the over-expression of plasma miR 106b~25 in GC.MethodsBased on 65 pairs matched GC patients and health controls, we explored clinical significance of miR 106b~25 for GC and compared their diagnostic performance with conventional tumor biomarkers including CA724, CA242, CA199 and CEA.ResultsBoth miR 106b~25 cluster and conventional tumor biomarkers were significantly elevated in GC (All P<0.05). In ROC curves, miR 106b had the highest AUC (0.898) in diagnosing GC with optimal sensitivity of 86.2% and specificity of 92.3% at the cut-off value of 1.385. MiR 25 had moderate diagnostic efficacy (AUC = 0.817) with sensitivity of 87.6% and specificity of 76.9% at the threshold of 1.015. The AUC of miR 93 (0.756) was the lowest. The AUC, sensitivity, accuracy and Youden index of miR 106b were higher than all of four conventional biomarkers, while its specificity is higher than CA242 and CA724. The AUC of miR 25 was also higher than CA724, CA242 and CA199, while AUC of miR 93 was only higher than CA199 and CA724. Compared the diagnostic efficacy via ROC curves, miR 106b was significantly higher diagnostic efficacy than CA724, CA242 and CA199, the diagnostic efficacies of miR 93 and miR 25 were significantly higher than CA199(all P<0.05).ConclusionsPlasma miR 106b~25 cluster, especially miR 106b, were significantly increased in GC patients and may be hopeful diagnostic biomarkers.

Chemotherapy is one of the main categories of clinical cancer treatment. One of the hindrances of a popularly used chemo-drug doxorubicin (DOX) is that some types of cancer cells are or become insensitive/resistant to DOX. In this work, we report a near-infrared (NIR) fluorescent turn-on probe DBT-2EEGYLFFVFER by conjugation of an environment-sensitive fluorophore DBT with human epidermal growth factor receptor 2 (HER2) specific binding peptides. Besides the NIR fluorescence turn-on signature, DBT-2EEGYLFFVFER also has activatable capability of reactive oxygen species (ROS) generation. DBT-2EEGYLFFVFER is weakly fluorescent in aqueous solution and hardly produces ROS under white light irradiation. However, both the NIR fluorescence and ROS production ability can be switched on when DBT-2EEGYLFFVFER binds to HER2 proteins overexpressed in cancer cells. Besides specific visualization of HER2-expressed cancer cells, DBT-2EEGYLFFVFER upon exposure to light is able to effectively increase the intracellular ROS level and offer an intracellular oxidative microenvironment, which does not cause the death of cancer cells, but greatly and synergistically boosts the cytotoxicity of DOX against HER2-expressed cancer cells with a supra-additive effect of "0 + 1 > 1".

When supramolecular hydrogels are applied as tissue culture scaffolds, their mechanical strength and biocompatibility are the two most important factors that must be considered. However, systematic studies on the structure-mechanical property (or structure-cytotoxicity) relationship of hydrogels are rare. Herein, we rationally designed three hydrogelators and their corresponding phosphate precursors, and systematically studied their self-assembling ability and cytotoxicity. The results indicated that fluorine substitution, but not trifluoromethyl substitution with more fluorine atoms, to the phenylalanine motif enhanced the self-assembling ability and cytotoxicity of the hydrogelators (or precursors). We envision that our preliminary study of hydrogelator fluorination would provide a strategy for the development of supramolecular hydrogels for wider biomedical applications.