Background and aims: The complex process of cancer metastasis remains the least understood. Tumor cells alter their protein expression profile to survive from the tumor metastasis. Fibronectin 1 (FN1 gene coding protein) is a member of the glycoprotein family that has been shown to play an important role in cancer metastasis. However, its effects on melanoma metastasis are still unclear. Methods: We detected the FN1 expression between metastatic cells and primary cells by using Western blot and RT-qPCR assays. And, we analyzed the expressed feature of FN1 in different tissues and examined the clinical relevance of upregulated FN1 in melanoma progression by bioinformatic analysis. Furthermore, we downregulated the expression of FN1 by small interfering RNA technique to reveal the effect of FN1 on melanoma phenotype and expression of related genes. Finally, we used bioinformatics to reveal the possible mechanism of FN1 regulating melanoma progression. Results: We reported that the expression of FN1 was changed during melanoma metastasis. In this study, we established two metastatic cell lines of melanoma through mouse model, and found that metastatic cells exhibited stronger mesenchyme phenotype and possessed higher FN1 expression level compared to primary cells. Besides, we examined the clinical relevance of upregulated FN1 in tumor progression. Small interfering RNA (siRNA)-mediated downregulation of FN1 suppressed the migration, invasion, adhesion, proliferation capabilities and induced apoptosis of melanoma cells. We detected a diminished EMT-related gene signature including increased expression of E-cadherin and decreased expression of N-cadherin and Vimentin. Downregulation of FN1 also increased Bax/Bcl-2 ratio which might result in apoptosis of melanoma cells. Bioinformatics analysis revealed that FN1 most likely involved in focal adhesion and PI3K-Akt signaling pathway to regulate EMT process and apoptosis. Conclusions: Taken together, these findings demonstrated a role of FN1 in promoting melanoma metastasis by inhibiting apoptosis and regulating EMT.

Metastasis is the leading cause of melanoma-related mortality. Current therapies are rarely curative for metastatic melanoma, revealing the urgent need to identify more effective preventive and therapeutic targets. This study aimed to screen the core genes and molecular mechanisms related to melanoma metastasis. A gene expression profile, GSE8401, including 31 primary melanoma and 52 metastatic melanoma clinical samples, was downloaded from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) between melanoma metastases and primary melanoma were screened using GEO2R tool. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genome (KEGG) analyses of DEGs were performed using the Database for Annotation Visualization and Integrated Discovery (DAVID). The Search Tool for the Retrieval of Interacting Genes (STRING) and Cytoscape with Molecular Complex Detection (MCODE) plug-in tools were utilized to detect the protein–protein interaction (PPI) network among DEGs. The top 10 genes with the highest degrees of the PPI network were defined as hub genes. In the results, 425 DEGs, including 60 upregulated genes and 365 downregulated genes, were identified. The upregulated genes were enriched in ECM–receptor interactions and the regulation of actin cytoskeleton, while 365 downregulated genes were enriched in amoebiasis, melanogenesis, and ECM–receptor interactions. The defined hub genes included CDK1, COL17A1, EGFR, DSG1, KRT14, FLG, CDH1, DSP, IVL, and KRT5. In addition, the mRNA and protein levels of the hub genes during melanoma metastasis were verified in the TCGA database and paired post- and premetastatic melanoma cells, respectively. Finally, KRT5-specific siRNAs were utilized to reduce the KRT5 expression in melanoma A375 cells. An MTT assay and a colony formation assay showed that KRT5 knockdown significantly promoted the proliferation of A375 cells. A Transwell assay further suggested that KRT5 knockdown significantly increased the cell migration and cell invasion of A375 cells. This bioinformatics study provided a deeper understanding of the molecular mechanisms of melanoma metastasis. The in vitro experiments showed that KRT5 played the inhibitory effects on melanoma metastasis. Therefore, KRT5 may serve important roles in melanoma metastasis.

The remarkable lubrication properties of normal articular cartilage play an essential role in daily life, providing almost frictionless movements of joints. Alterations of cartilage surface or degradation of biomacromolecules within synovial fluid increase the wear and tear of the cartilage and hence determining the onset of the most common joint disease, osteoarthritis (OA). The irreversible and progressive degradation of articular cartilage is the hallmark of OA. Considering the absence of effective options to treat OA, the mechanosensitivity of chondrocytes has captured attention. As the only embedded cells in cartilage, the metabolism of chondrocytes is essential in maintaining homeostasis of cartilage, which triggers motivations to understand what is behind the low friction of cartilage and develop biolubrication-based strategies to postpone or even possibly heal OA. This review firstly focuses on the mechanism of cartilage lubrication, particularly on boundary lubrication. Then the mechanotransduction (especially shear stress) of chondrocytes is discussed. The following summarizes the recent development of cartilage-inspired biolubricants to highlight the correlation between cartilage lubrication and OA. One might expect that the restoration of cartilage lubrication at the early stage of OA could potentially promote the regeneration of cartilage and reverse its pathology to cure OA.

Three new angucycline-type C-glycosides, grincamycins L–N (1–3), together with the known rabelomycin (4), moromycin B (5), fridamycin D (6), saquayamycin B1 (7), actinomycin X₂ (8), and actinomycin D (9), were isolated from the culture of the soil-derived Streptomyces sp. XZHG99T collected from Color desert, Dengpa District, Tibet. The structures of 1–3 were established by detailed analyses of comprehensive spectroscopic data. Compounds 1–9 exhibited significant cytotoxicity against a panel of human cancer cell lines A549, H157, MCF7, MDA-MB-231, and HepG2, while 4, 8, and 9 showed decent antibacterial activity against Mycobacterium smegmatis and Staphylococcus aureus.