Identification of a metabolism-linked genomic signature for prognosis and immunotherapeutic efficiency in metastatic skin cutaneous melanoma.

Metastatic skin cutaneous melanoma (MSCM) is the most rapidly progressing/invasive skin-based malignancy, with median survival rates of about 12 months. It appears that metabolic disorders accelerate disease progression. However, correlations between metabolism-linked genes (MRGs) and prognosis in MSCM are unclear, and potential mechanisms explaining the correlation are unknown. The Cancer Genome Atlas (TCGA) was utilized as a training set to develop a genomic signature based on the differentially expressed MRGs (DE-MRGs) between primary skin cutaneous melanoma (PSCM) and MSCM. The Gene Expression Omnibus (GEO) was utilized as a validation set to verify the effectiveness of genomic signature. In addition, a nomogram was established to predict overall survival based on genomic signature and other clinic-based characteristics. Moreover, this study investigated the correlations between genomic signature and tumor micro-environment (TME). This study established a genomic signature consisting of 3 genes (CD38, DHRS3, and TYRP1) and classified MSCM patients into low and high-risk cohorts based on the median risk scores of MSCM cases. It was discovered that cases in the high-risk cohort had significantly lower survival than cases in the low-risk cohort across all sets. Furthermore, a nomogram containing this genomic signature and clinic-based parameters was developed and demonstrated high efficiency in predicting MSCM case survival times. Interestingly, Gene Set Variation Analysis results indicated that the genomic signature was involved in immune-related physiological processes. In addition, this study discovered that risk scoring was negatively correlated with immune-based cellular infiltrations in the TME and critical immune-based checkpoint expression profiles, indicating that favorable prognosis may be influenced in part by immunologically protective micro-environments. A novel 3-genomic signature was found to be reliable for predicting MSCM outcomes and may facilitate personalized immunotherapy.

Knockdown of circMYOF inhibits cell growth, metastasis, and glycolysis through miR-145-5p/OTX1 regulatory axis in laryngeal squamous cell carcinoma.

New evidence suggests that abnormal expression of circular RNA (circRNA) is associated with the development of human cancers. This study aims to reveal circMYOF roles in the malignant phenotype of laryngeal squamous cell carcinoma (LSCC). The expression of circMYOF, microRNA (miR)-145-5p, and orthodenticle homeobox 1 (OTX1) was detected by quantitative real-time PCR. Cell proliferation, migration, invasion, and apoptosis were determined using colony formation assay and EdU assay, wound healing assay, transwell assay, and flow cytometry, respectively. Protein expression was examined by western blot analysis. Cell glycolysis was assessed by detecting glucose consumption and lactate production. Mice xenograft models were constructed to evaluate the regulation of circMYOF on LSCC tumorigenesis. The regulatory relationships among circMYOF, miR-145-5p, and OTX1 were identified using dual-luciferase reporter assay and RIP assay. Serum exosomes were isolated to confirm the existence of circMYOF in LSCC patients. CircMYOF was upregulated in LSCC tissues and cells, and its knockdown suppressed LSCC cell growth, metastasis, and glycolysis, as well as inhibited LSCC tumor growth. MiR-145-5p had decreased expression in LSCC, and it could be sponged by circMYOF. The inhibition effect of circMYOF lentivirus short hairpin RNA (sh-circMYOF) on LSCC progression was restored by the inhibitor of miR-145-5p (in-miR-145-5p). Also, OTX1 was targeted by miR-145-5p and was positively regulated by circMYOF. MiR-145-5p could repress LSCC progression, and OTX1 overexpression also eliminated this effect. In addition, we found that circMYOF was significantly overexpressed in the serum exosomes of LSCC patients. Our data revealed that circMYOF contributed to LSCC progression by promoting cell growth, metastasis, and glycolysis through miR-145-5p/OTX1 axis.

C18H17NO6 Inhibits Invasion and Migration of Human MNNG Osteosarcoma Cells via the PI3K/AKT Signaling Pathway.

BACKGROUND Osteosarcoma (OS) is a highly aggressive, metastatic bone tumor with a poor prognosis, and occurs more commonly in children and adolescents. Therefore, new drugs and treatments are urgently needed. In this study, we investigated the effect and potential mechanisms of C18H17NO6 on osteosarcoma cells. MATERIAL AND METHODS Human MNNG osteosarcoma cells were treated with different concentrations of C18H17NO6. The proliferation of the MNNG cells was examined via CCK-8 assay. Cell migration and invasion were tested via wound-healing assay and Transwell migration and invasion assays. ELISA was used to detect MMP-2, MMP-9, and VEGF secretion. Finally, Western blotting and qRT-PCR were used to detect protein and mRNA expressions, respectively. RESULTS C18H17NO6 inhibited MNNG proliferation in a dose- and time-dependent manner and inhibited MMP-2, MMP-9, and VEGF secretion. C18H17NO6 treatment significantly downregulated N-cadherin and Vimentin expression levels and upregulated E-cadherin expression levels in vitro and in vivo. C18H17NO6 inhibited tumor growth in a MNNG xenograft. We also found that C18H17NO6 can significantly reduce the phosphorylation of the PI3K/AKT signaling pathway in vivo and in vitro. However, 740Y-P (a PI3K agonist) had the opposite effect on proliferation, migration and invasion of MNNG cells treated with C18H17NO6. LY294002 (a PI3K inhibitor) downregulated p-PI3K and p-AKT could mimic the inhibitory effect of C18H17NO6. CONCLUSIONS Our results suggest that C18H17NO6 can inhibit human MNNG osteosarcoma cell invasion and migration via the PI3K/AKT signaling pathway both in vivo and in vitro. C18H17NO6 may be a highly effective and low-toxicity natural drug for the prevention or treatment of OS.