We developed a colorimetric sensor array with reported protein aptamers as nonspecific receptors. We found that different target proteins could make the aptamer-protected gold nanoparticles (AuNPs) exhibit different aggregation behaviors in the presence of a high concentration salt and cause various color change. On the basis of this phenomenon, we applied a series of reported protein aptamers as a receptor array obtaining a distinct response pattern to each target protein. Seven proteins have been well distinguished with the naked eye at the 50 nM level. Cancerous human cells have also been discriminated from noncancerous cells. This method is simple, label-free, and sensitive. It will broaden the application filed of plasmonic nanoparticle-based sensors and give a new direction of developing sensitive array sensing systems.

We constructed a DNA tetrahedron based multicolor nanoprobe, which could simultaneously imaging of three tumor-related mRNAs in living cells through fluorescence restoration caused by competitive chain replacement reaction. The oligonucleotides used to construct the tetrahedron were extended by adding three 21-base recognition sequences modified with different fluorophores (FAM, Cy3, and Cy5) in the 5' end. Three 11-base complementary sequences modified with quencher (BHQ1 for FAM and BHQ2 for Cy3 and Cy5) were hybridized with the recognition sequences to quench the fluorescence. In the presence of the specific mRNA targets, the recognition sequences hybridized with the targets to form longer duplexes and the fluorescence was restored. Compared with previously reported nanoprobes based on DNA tetrahedron, the multicolor nanoprobe can effectively avoid false positive results.

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Background Synonymous mutations do not change the protein sequences. Automatically, they have been regarded as neutral events and are ignored in the mutation-based cancer studies. However, synonymous mutations will change the codon optimality, resulting in altered translational velocity. Methods We fully utilized the transcriptome and translatome of liver cancer and normal tissue from ten patients. We profiled the mutation spectrum and examined the effect of synonymous mutations on translational velocity. Results Synonymous mutations that increase the codon optimality significantly enhanced the translational velocity, and were enriched in oncogenes. Meanwhile, synonymous mutations decreasing codon optimality slowed down translation, and were enriched in tumor suppressor genes. These synonymous mutations significantly contributed to the translational changes in tumor samples compared to normal samples. Conclusions Synonymous mutations might play a role in liver cancer development by altering codon optimality and translational velocity. Synonymous mutations should no longer be ignored in the genome-wide studies.

This study aimed at determining the role of hsa-let-7e-5p in the progression of head and neck squamous cell carcinoma (HNSCC). The relative levels of hsa-let-7e-5p transcripts in 15 paired of HNSCC and adjacent non-tumor tissues and cells were examined by quantitative real-time PCR (qRT-PCR). The potential targets of hsa-let-7e-5p were predicted and validated by luciferase assay. The impact of altered hsa-let-7e-5p expression on HNSCC cell proliferation and metastasis was determined by CCK-8, wound healing, transwell migration and invasion assays. The effect of hsa-let-7e-5p over-expression on the growth of HNSCC was examined in vivo . Hsa-let-7e-5p expression was significantly down-regulated in HNSCC tissues and highly metastatic PCI-37B cells. Bioinformatic analysis predicted that hsa-let-7e-5p bound to the 3'untranslated region (3'UTR) of chemokine receptor 7(CCR7), which was validated by luciferase assay. While transfection with hsa-let-7e-5p mimic significantly decreased CCR7 protein expression, transfection with hsa-let-7e-5p inhibitor increased CCR7 protein expression in HNSCC cells. Similarly, hsa-let-7e-5p over-expression inhibited PCI-37B cell proliferation, wound healing, migration and invasion, while inhibition of endogenous hsa-let-7e-5p had opposite effects in PCI-37A cells. Hsa-let-7e-5p over-expression inhibited PCI-37B tumor growth in vivo . Therefore, hsa-let-7e-5p acts as a tumor suppressor to inhibit the progression of HNSCC by targeting CCR7 expression. Hsa-let-7e-5p and CCR7 may be therapeutic targets of HNSCC.

The discrimination of the type of cancer cells remains challenging due to the subtle differences in their expression of membrane receptors. In this work, we developed a multicolor cell imaging method for distinguishing the type of cancer cells with fluorophore-tagged aptamers. We found that the interaction between aptamers and cancer cells was affected by both of the sequence of aptamers and the labeled dyes. As the co-ownership of biomarkers for different cancer cell lines, the fluorophore-tagged aptamers interacted with different cancer cell lines in different degree, resulting in a distinct color to discriminate the type of cancer cells at single cell level. Taking advantage of the cross-reactive ability of the fluorophore-tagged aptamers, we could not only distinguish the cancerous cells quickly from large quantities of noncancerous cells, but also identify the type of the cancerous cells. This work has potential application for cancer diagnostic and therapy in the future.

Protein tyrosine phosphatase 1B (PTP1B) has become an outstanding target for the treatment of diabetes and obesity. Recent research has demonstrated that some fullerene derivatives serve as a new nanoscale-class of potent inhibitors of PTP1B, but the specific mechanism remains unclear. Several molecular modeling methods (molecular docking, molecular dynamics simulations, and molecular mechanics/generalized Born surface area calculations) were integrated to provide insight into the binding mode and inhibitory mechanism of the new class of fullerene inhibitors. The results reveal that PTP1B with an open WPD loop is more susceptible to the combination with the fullerene inhibitor because of their comparable shapes and sizes. When the WPD loop fluctuates to the open conformation, the inhibitor falls into the active pocket and induces conformational rotation of the WPD loop. This rotation is closely related to the reduction of the catalytic activity of PTP1B. In addition, it is suggested that compound 1, like compound 2, is a competitive inhibitor since it blocks the active site to prevent the binding of the substrate. The high binding affinity of fullerene-based compounds and the transition of the WPD loop, caused by the specific structural property of the hydrophobic fullerene core and the appended polar groups, make these fullerene derivatives efficient competitive inhibitors. The theoretical results provide useful clues for further investigation of the noval inhibitors of PTP1B at the nanoscale.

microRNAs (miRNAs), a family of small non-coding RNA molecules, are implicated in cancer growth and progression. In the present study, we examined the expression and biological roles of miR-590 in non-small cell lung cancer (NSCLC). Compared to normal lung tissues, miR-590 expression was downregulated in primary NSCLCs and, to a greater extent, in corresponding brain metastases. NSCLC cell lines with high metastatic potential had significantly (P < 0.05) lower levels of miR-590 than those with low metastatic potential. Re-expression of miR-590 suppressed NSCLC cell proliferation, colony formation, migration, and invasion in vitro and tumorigenesis in vivo. In contrast, inhibition of miR-590 enhanced the migration and invasion of NSCLC cells. Mechanistic studies revealed that a disintegrin and metalloproteinase 9 (ADAM9) was a direct target of miR-590. Delivery of miR-590 mimic was found to decrease endogenous ADAM9 expression in NSCLC cells. Enforced expression of a miRNA-resistant form of ADAM9 significantly restored the aggressive behaviors in miR-590-overexpressing NSCLC cells. Taken together, our data reveal miR-590 as a tumor suppressor in NSCLC, which is at least partially mediated through targeting of ADAM9. Restoration of miR-590 may provide a promising therapeutic strategy for NSCLC.