PARK7/DJ-1 inhibition decreases invasion and proliferation of uveal melanoma cells

Introduction: PARK7/DJ-1 is an oncogene that is associated with tumorigenesis in many cancers. Recent studies have demonstrated the importance of DJ-1 in the origin and development of uveal melanoma (UM). We present an analysis of the role of the DJ-1 protein in UM cells, especially in its effect on proliferation and migration. Methods: UM cells from a primary tumor, Mel 270, and its liver metastasis, OMM2.5, were transfected with lentiviral-delivered shRNA against PARK7/DJ-1. Evaluation of cell migration and proliferation was performed using the xCELLigence real-time cell analyzer (RTCA). The effect of DJ-1 inhibition on the PTEN-Akt signaling pathway was also studied by immunoblotting. Results: The silencing of PARK7/DJ-1 oncoprotein expression produced a significant decrease of phosphorylated Akt (S473) in Mel270 and in metastatic OMM2.5 UM cells with no alteration on tumor suppressor PTEN expression. The diminution of PARK7/DJ-1 expression significantly inhibited real-time proliferation and invasion of Mel270 and OMM2.5 and the invasion potential of the metastatic cells. Conclusion: DJ-1 appears to play a key role on the PTEN/Akt pathway in UM. DJ-1 inhibition appears to have a negative effect on proliferation and invasion of UM cells. This suggests DJ-1 as a potential therapeutic target in UM.

New Frontiers in Peripheral Nerve Regeneration: Concerns and Remedies

Topical advances in studying molecular and cellular mechanisms responsible for regeneration in the peripheral nervous system have highlighted the ability of the nervous system to repair itself. Still, serious injuries represent a challenge for the morphological and functional regeneration of peripheral nerves, calling for new treatment strategies that maximize nerve regeneration and recovery. This review presents the canonical view of the basic mechanisms of nerve regeneration and novel data on the role of exosomes and their transferred microRNAs in intracellular communication, regulation of axonal growth, Schwann cell migration and proliferation, and stromal cell functioning. An integrated comprehensive understanding of the current mechanistic underpinnings will open the venue for developing new clinical strategies to ensure full regeneration in the peripheral nervous system.

Molecular Mechanism of Gas Anesthetics on the Invasion, Metastasis, and Chemosensitivity of Osteosarcoma Cells

Background. Osteosarcoma is one of the most prominent bone cancers which has a predominant occurrence in children and adolescents. This study is focused on determining the effects of treatment of gas anesthetics on invasion, metastasis, and chemosensitivity in the progression of osteosarcoma cells. Material and Methods. The biological effects of the common gas anesthetics—desflurane, isoflurane, and sevoflurane—on osteosarcoma cells were studied and compared. The biological assays were performed for analysis of cell migration and proliferation. Results. Isoflurane and sevoflurane have shown significant inhibition in the osteosarcoma cells at clinically relevant concentrations. Desflurane has shown less potent action on cell migration and inhibition. All three gas anesthetics have shown inhibition in cell proliferation. The effective antiproliferative action was at a clinically significant dose. At low millimolar concentrations, cell apoptosis was moderately affected. Drug combination analysis with chemotherapeutic drugs showed relevant inhibition in cell migration. All three agents showed significant augmentation of chemotherapeutic drugs in suppression and inhibition of inducing apoptosis. The antimigration action is likely to affect the PI3K/AKT pathway and IGF-1. Conclusion. The study demonstrates the proposed mechanisms of gas anesthetics and their differential effects on osteosarcoma cells and their survival, migration, growth, and chemosensitivity.

The H3K27 demethylase controls the lateral line embryogenesis of zebrafish

Background Kdm6b, a specific histone 3 lysine 27 (H3K27) demethylase, has been reported to be implicated in a variety of developmental processes including cell differentiation and cell fate determination and multiple organogenesis. Here, we regulated the transcript level of kdm6bb to study the potential role in controlling the hearing organ development of zebrafish. Methods A morpholino antisense oligonucleotide (MO) strategy was used to induce Kdm6b deficiency; immunohistochemical staining and in situ hybridization analysis were conducted to figure out the morphologic alterations and embryonic mechanisms. Results Kdm6bb is expressed in the primordium and neuromasts at the early stage of zebrafish embryogenesis, suggesting a potential function of Kdm6b in the development of mechanosensory organs. Knockdown of kdm6bb severely influences the cell migration and proliferation in posterior lateral line primordium, abates the number of neuromasts along the trunk, and mRNA-mediated rescue test can partially renew the neuromasts. Loss of kdm6bb might be related to aberrant expressions of chemokine genes encompassing cxcl12a and cxcr4b/cxcr7b in the migrating primordium. Moreover, inhibition of kdm6bb reduces the expression of genes in Fgf signaling pathway, while it increases the axin2 and lef1 expression level of Wnt/β-catenin signaling during the migrating stage. Conclusions Collectively, our results revealed that Kdm6b plays an essential role in guiding the migration of primordium and in regulating the deposition of zebrafish neuromasts by mediating the gene expression of chemokines and Wnt and Fgf signaling pathway. Since histone methylation and demethylation are reversible, targeting Kdm6b may present as a novel therapeutic regimen for hearing disorders.

Development of Antimicrobial Conjugates and Evaluating its Antibacterial potential and Wound Healing ability

Antimicrobial peptides from Streptomyces sp. and marine fish (Carangoides malabaricus) were extracted and developed as conjugates in the present study. The objective was framed to analyze the ability of conjugate to retard the growth of test bacteria causing diabetic foot ulcers. Fibroblast cell adhesion on AMP conjugates coated mesh samples were recorded using microscopic studies with an aim of developing a novel tissue engineered wound dressing material. Thus developed tissue engineered materials were evaluated for its antibacterial potential against wound pathogens; and to assay the wound healing ability using a standard in vitro wound scratch method. Tissue engineered materials were developed using L929 fibroblast cells. L929 fibroblast cells attachment and its stage wise development on wound dressing mesh materials were microscopically observed. In vitro wound healing assay revealed that the developed conjugates (containing AMPs) exhibited cell migration and proliferation after 12th hour of incubation indicating the wound healing abilities. The results showed that the developed tissue engineered wound dressing material has commercial interest in near future.

Upregulation of HOX genes promotes cell migration and proliferation in head and neck squamous cell carcinoma

BACKGROUND: Expression dysregulation of HOX homeobox genes has been observed in several cancers, including head and neck squamous cell carcinoma (HNSC). Although characterization of HOX gene roles in HNSC development has been reported, there is still a need to better understand their real contribution to tumorigenesis. OBJECTIVE: The present study aimed to evaluate the contribution of the protein-coding HOX genes (HOXA10, HOXC9, HOXC10, and HOXC13) in cellular processes related to carcinogenesis and progression of the HNSC. METHODS: Expression of HOX genes was analyzed in HNSC RNA-Seq data from The Cancer Genome Atlas (TCGA) and by RT-qPCR in different tumor cell lines. siRNA-mediated knockdown of HOXA10, HOXC9, HOXC10 or HOXC13 was performed in HNSC cell lines, and predicted transcriptional targets HOX genes was analyzed by bioinformatic. RESULTS: Thirty-one out of the 39 mammalian HOX genes were found upregulated in HNSC tissues and cell lines. The HOXC9, HOXC10 or HOXC13 knockdown attenuated cell migration, and lead to downregulation of epithelial-mesenchymal transition (EMT) markers, which were predicted as transcriptional targets of these three HOX genes. Diminished colony formation and cell cycle arrest after HOXC10 or HOXC13 knockdown were also observed, corroborating the fact that there was an enrichment for genes in proliferation/cell cycle pathways. CONCLUSIONS: In summary, we revealed roles for HOXC9, HOXC10, and HOXC13 in cell migration and proliferation/cell cycle progression in HNSC cells and suggested that those HOX members contribute to HNSC development possibly by regulating tumor growth and metastasis.