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Using nanomaterials to achieve functional enzyme mimics (nanozymes) is attractive for both applied and fundamental research. Laccases are multicopper oxidases highly important for biotechnology and environmental remediation. In this work, we report an exceptionally simple yet functional laccase mimic based on guanosine monophosphate (GMP) coordinated copper. It forms an amorphous metal-organic framework (MOF) material. The ratio of copper and GMP is 3:4 as determined by isothermal titration calorimetry. It has excellent laccase-like activity and converts a diverse range of phenol containing substrates such as hydroquinone, naphthol, catechol and epinephrine. Comparative work shows that the activity is originated from guanosine coordination instead of phosphate binding in GMP. Cu is required and cannot be substituted by other metal ions. At the same mass concentration, the Cu/GMP nanozyme has a higher V and similar K compared to the protein laccase. To achieve the same catalytic efficiency, the cost of the Gu/GMP is ∼2400-fold lower than that of laccase. The Cu/GMP is much more stable at extreme pH, high salt, high temperature and for long-term storage. This is one of the first laccase-mimicking nanozymes, which will find important applications in analytical chemistry, environmental protection, and biotechnology.

Background: MALAT1, a highly conserved long non-coding RNA (lncRNA), acts as oncogene in multiple human cancers. Results: miR-101 and miR-217 can silence MALAT1 expression and then inhibit esophageal cancer proliferation, migration and invasion. Conclusion: Tumor suppressor miR-101 and miR-217 can negatively regulate MALAT1 expression. Significance: These data provide a new mechanism for MALAT1 regulation.

Long noncoding RNA (lncRNA) HOX transcript antisense RNA (HOTAIR), which could induce genome-wide retargeting of polycomb-repressive complex 2, trimethylates histone H3 lysine-27 (H3K27me3) and deregulation of multiple downstream genes, is involved in development and progression of esophageal squamous cell carcinoma (ESCC). We hypothesized that the functional single nucleotide polymorphisms (SNP) in HOTAIR may affect HOTAIR expression and/or its function and, thus, ESCC risk. Therefore, we examined the association between three haplotypetagging SNPs (htSNP) across the whole HOTAIR locus and ESCC risk as well as the functional relevance of an ESCC susceptibility SNP rs920778. Genotypes were determined in three independent case-control sets consisted of 2098 ESCC patients and 2150 controls. The allele-specific regulation on HOTAIR expression by the rs920778 SNP was investigated in vitro and in vivo. We found that the HOTAIR rs920778 TT carriers had a 1.37-fold, 1.78-fold and 2.08-fold increased ESCC risk in Jinan, Shijiazhuang and Huaian populations, respectively, compared with the CC carriers (P = 0.003, 7.7 × 10 -4 and 5.9 × 10 -4). During inspecting functional relevance of the rs920778 SNP, we identified a novel intronic HOTAIR enhancer locating between +1719bp and +2353bp from the transcriptional start site through reporter assays. Moreover, there is an allelic regulation of rs920778 on HOTAIR expression via this enhancer in both ESCC cell lines and normal esophageal tissue specimens, with higher HOTAIR expression among T allele carriers. These results demonstrate that functional genetic variants influencing lncRNA regulation may explain a fraction of ESCC genetic basis.

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