Inhibiting lncRNA NEAT1 facilitates the sensitization of melanoma cells to cisplatin through modulating the miR-519c-3p-MeCP2 axis.

Cutaneous melanoma is an aggressive human malignancy, leading to high mortality worldwide. In addition to surgery, radiotherapy and chemotherapy are routine approaches to treat melanoma at late or metastatic stage. However, a group of melanoma patients developed chemoresistance, which ultimately limited the efficiency of chemotherapy. LncRNA NEAT1 (Nuclear-enriched abundant transcript 1) is frequently overexpressed in various cancers. Currently, the precise roles and underlying mechanisms of NEAT1 in chemoresistant melanoma remain unclear. This study reports NEAT1 was significantly upregulated in melanoma tumor specimens and cell lines. Blocking NEAT1 effectively sensitized melanoma cells to cisplatin (CDDP), a frequently used first-line anticancer agent. From the established cisplatin resistant melanoma cell line (SK-MEL-5 CDDP Res), we detected significantly upregulated NEAT1 expression and downregulated miR-519c-3p expression compared with those from SK-MEL-5 parental cells. Subsequently, expression of miR-519c-3p was remarkedly attenuated in melanoma tumors and cell lines. Bioinformatics analysis, RNA pull-down assay and luciferase assay consistently demonstrated that NEAT1 sponged miR-519c-3p to downregulate its expression in melanoma cells. Moreover, we identified the methyl CpG binding protein 2 (MeCP2), which is positively associated with cisplatin resistance in melanoma, was a direct target of miR-519c-3p in melanoma cells. Restoration of MeCP2 rescued the miR-519c-3p-promoted cisplatin sensitization. Finally, we showed restoration of miR-519c-3p in NEAT1-overexpressing SK-MEL-5 CDDP Res cells successfully overrode the NEAT1-promoted cisplatin resistance in melanoma from in vitro and in vivo results. In summary, our results unveiled biological roles and molecular mechanisms of the noncoding RNA-mediated cisplatin resistance in melanoma, suggesting blocking the NEAT1-miR-519c-3p-MeCP2 axis as a therapeutic strategy against chemoresistant melanoma.

Phylogenetic implications of mitogenome rearrangements in East Asian potamiscine freshwater crabs (Brachyura: Potamidae).

We present here a combined mitogenome gene order dataset totalling 62% of the known genera of East Asian potamiscine freshwater crabs that includes first-time mitogenome data for 14 species and gene order data from 37 other species of potamiscines. A surprisingly high number of mitogenome gene order rearrangements were found in the taxa studied (comprising nine different rearrangements and seven major patterns, one of which has two sub-arrangements). Our phylogenetic reconstructions indicate that the mitogenome gene order rearrangements are associated with the evolutionary history of potamiscine lineages. We also used a new Event-based Maximum Parsimony method to reconstruct ancestral gene orders, which takes into consideration gene duplication, pseudogeneticization, and tandem duplication random loss. Furthermore, shared mitogenome gene order patterns were used to inform the taxonomic placement of Sinopotamon parvum, and the cryptic diversity in Potamiscus. The remarkably frequent mitogenome rearrangements in potamiscine freshwater crabs have great potential to contribute to our understanding of the evolutionary history of these highly diverse decapods in East Asia.

Complete mitochondrial genome of the San Lucan gecko, Phyllodactylus unctus (Sauria, Gekkota, Phyllodactylidae), in comparison with Tarentola mauritanica.

We sequenced the complete mitochondrial genome of the San Lucan gecko, Phyllodactylus unctus, which is endemic to Mexico. The complete mitochondrial genome was 16,881 bp in size, consisting of 37 genes coding for 13 proteins, 2 rRNAs, 22 tRNAs and 1 control region. Its gene arrangement pattern was identical with most vertebrates. We compared the mitochondrial genome of P. unctus with that of the Moorish gecko, Tarentola mauritanica, which is the only other sequenced species from Phyllodactylidae. Nucleotide sequence divergence (p distance) between two mitochondrial genomes was 31.32%. The detailed comparison between the mitochondrial genomes of two species was done.

Glutathione-triggered formation of molecular hydrogels for 3D cell culture.

The development of three dimensional (3D) scaffolds that are suitable for cell encapsulation and proliferation is highly important for tissue engineering and regenerative medicine. We reported in this paper on several molecular hydrogels formed through glutathione (GSH) reduction, whose mechanical property and zeta potential could be regulated by concentration and structure of gelators in resulting gels, respectively. The hydrogels were characterized by several techniques including rheology, TEM and fluorescence. We found that, in our system, the mechanical property of hydrogels but not the zeta potential of self-assembled structures had big influences on mouse fibroblast 3T3 cells spreading and proliferation. Hydrogels with storage modulus (G') of hundreds of pascals (Pa) were suitable for 3T3 cells spreading and proliferation. We believed that hydrogels reported in this study had big potential for applications in different fields, such as 3D cell culture and tissue engineering.