A signature of seven hypoxia-related lncRNAs is a potential biomarker for predicting the prognosis of melanoma.

Melanoma is the most aggressive type of skin cancer and has a high mortality rate once metastasis occurs. Hypoxia is a universal characteristic of the microenvironment of cancer and a driver of melanoma progression. In recent years, long noncoding RNAs (lncRNAs) have attracted widespread attention in oncology research. In this study, screening was performed and revealed seven hypoxia-related lncRNAs AC008687.3, AC009495.1, AC245128.3, AL512363.1, LINC00518, LINC02416 and MCCC1-AS1 as predictive biomarkers. A predictive risk model was constructed via univariate Cox regression analysis, least absolute shrinkage and selection operator (LASSO), and multivariate Cox regression analyses. Patients were grouped according to the model risk score, and Kaplan-Meier analysis was performed to compare survival between groups. Functional and pathway enrichment analyses were performed to compare gene set enrichment between groups. Moreover, a nomogram was constructed with the risk score as a variable. In both the training and validation sets, patients in the low-risk group had better overall survival than did those in the high-risk group (P<0.001). The 3-, 5- and 10-year area under the curve (AUC) values for the nomogram model were 0.821, 0.795 and 0.820, respectively. Analyses of immune checkpoints, immunotherapy response, drug sensitivity, and mutation landscape were also performed. The results suggested that the low-risk group had a better response to immunotherapeutic. In addition, the nomogram can effectively predict the prognosis and immunotherapy response of melanoma patients. The signature of seven hypoxia-related lncRNAs showed great potential value as an immunotherapy response biomarker, and these lncRNAs might be treatment targets for melanoma patients.

Influenza A Virus Production in Mouse Lung Is Inhibited by Inhalation of Aerosol Polyethylenimine/Short Hairpin RNA Plasmid Complexes.

Influenza pandemics are a global threat to human health, with existing vaccines and antiviral drugs providing limited protection. There is an urgent need for new prophylactic and treatment strategies. In this study, 12 short hairpin (sh)RNAs targeting conserved regions of influenza A virus (IAV) matrix protein (M)2, nucleocapsid protein (NP), nonstructural protein (NS), and polymerase acidic (PA) were synthesized, and their effects on IAV replication in cells were investigated using Madin-Darby canine kidney (MDCK) cells transfected with the shRNA plasmids. Additionally, mice were administered a polyethyleneimine PEI/pLKD-NP-391 complex in aerosol form and then infected with AIV, and viral particles in the mouse lung were detected. IAV production was markedly lower in MDCK cells transfected with pLKD-M-121, pLKD-M-935, pLKD-NP-391, pLKD-NP-1291, pLKD-PA-1365, and pLKD-PA-1645 plasmids than in control cells (p < 0.01). The viral load in MDCK cells was decreased by transfection of plasmids pLKD-M-121 (p < 0.05) and pLKD-M-935, pLKD-NP-391, pLKD-NP-1291, pLKD-PA-1365, and pLKD PA-1645 (p < 0.01) compared to an empty plasmid. The viral load was significantly lower in the lungs of mice transfected with pLKD-NP-391 than in the control plasmid and mock transfection groups (p < 0.01 and p < 0.05, respectively). Thus, IAV production was inhibited by shRNAs targeting matrix IAV components; moreover, inhalation of a PEI/pLKD-NP-391 complex in aerosol form suppressed IAV production in infected mice. Thus, these shRNAs can be effective for the prevention and treatment of influenza virus infection.