Psoriasis is characterized by keratinocyte proliferation and immune cell infiltration. M2 isoform of pyruvate kinase (PKM2) was reported to have an important role in cell proliferation, which is a rate-limiting enzyme that regulates the final step of glycolysis. However, how PKM2 regulates cell metabolism and proliferation in psoriatic keratinocytes is still poorly understood. Interestingly, we found that PKM2 was highly expressed in psoriatic epidermis from patients and mouse models. PKM2 overexpression promoted keratinocyte glycolytic metabolism while knockdown inhibited keratinocyte proliferation and glycolysis. Mice lacking PKM2 specifically in keratinocytes, pharmacological inhibition of PKM2 or glycolysis inhibited keratinocyte proliferation and showed obvious remission in an imiquimod-induced psoriatic mouse model. Moreover, the inhibitor of the EGF-receptor blocked EGF-stimulated PKM2 expression and glycolysis in keratinocytes. We identify PKM2 as an upregulated gene in psoriasis. PKM2 is essential in keratinocyte over-proliferation and may represent a therapeutic target for psoriasis.

Metastasis is the most lethal stage of cancer progression. The present study aimed to investigate the underlying molecular mechanisms of melanoma metastasis using bioinformatics. Using the microarray dataset GSE8401 from the Gene Expression Omnibus database, which included 52 biopsy specimens from patients with melanoma metastasis and 31 biopsy specimens from patients with primary melanoma, differentially expressed genes (DEGs) were identified, subsequent to data preprocessing with the affy package, followed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. A protein-protein interaction (PPI) network was constructed. Mutated genes were analyzed with 80 mutated cases with melanoma from The Cancer Genome Atlas. The overall survival of key candidate DEGs, which were within a filtering of degree >30 criteria in the PPI network and involved three or more KEGG signaling pathways, and genes with a high mutation frequency were delineated. The expression analysis of key candidate DEGs, mutant genes and their associated genes were performed on UALCAN. Of the 1,187 DEGs obtained, 505 were upregulated and 682 were downregulated. ‘Extracellular exosome’ processes, the ‘amoebiasis’ pathway, the ‘ECM-receptor interaction’ pathway and the ‘focal adhesion’ signaling pathway were significantly enriched and identified as important processes or signaling pathways. The overall survival analysis of phosphoinositide-3-kinase regulator subunit 3 ( PIK3R3 ), centromere protein M ( CENPM ), aurora kinase A ( AURKA ), laminin subunit α 1 ( LAMA1 ), proliferating cell nuclear antigen ( PCNA ), adenylate cyclase 1 ( ADCY1 ), BUB1 mitotic checkpoint serine/threonine kinase ( BUB1 ), NDC80 kinetochore complex component ( NDC80 ) and protein kinase C α ( PRKCA ) in DEGs was statistically significant. Mutation gene analysis identified that BRCA1-associated protein 1 ( BAP1 ) had a higher mutation frequency and survival analysis, and its associated genes in the BAP1 -associated PPI network, including ASXL transcriptional regulator 1 ( ASXL1 ), proteasome 26S subunit, non-ATPase 3 ( PSMD3 ), proteasome 26S subunit, non ATPase 11 ( PSMD11 ) and ubiquitin C ( UBC ), were statistically significantly associated with the overall survival of patients with melanoma. The expression levels of PRKCA, BUB1, BAP1 and ASXL1 were significantly different between primary melanoma and metastatic melanoma. Based on the present study, ‘extracellular exosome’ processes, ‘amoebiasis’ pathways, ‘ECM-receptor interaction’ pathways and ‘focal adhesion’ signaling pathways may be important in the formation of metastases from melanoma. Th...

Background As the second most common malignancy in adults, papillary renal cell carcinoma (PRCC) has shown an increasing trend in both incidence and mortality. Effective treatment for advanced metastatic PRCC is still lacking. In this study, we aimed to establish competitive endogenous RNA (ceRNA) networks related to PRCC tumorigenesis, and analyze the specific role of differentially expressed ceRNA components and infiltrating immune cells in tumorigenesis. Methods CeRNA networks were established to identify the key ceRNAs related to PRCC tumorigenesis based on the 318 samples from The Cancer Genome Atlas database (TCGA), including 285 PRCC and 33 normal control samples. The R package, “CIBERSORT,” was used to evaluate the infiltration of 22 types of immune cells. Then we identified the significant ceRNAs and immune cells, based on which two nomograms were obtained for predicting the prognosis in PRCC patients. Finally, we investigated the co‐expression of PRCC‐specific immune cells and core ceRNAs via Pearson correlation test. Results COL1A1, H19, ITPKB, LDLR, TCF4, and WNK3 were identified as hub genes in ceRNA networks. Four prognostic‐related tumor‐infiltrating immune cells, including T cells CD4 memory resting, Macrophages M1, and Macrophages M2 were revealed. Pearson correlation test indicated that Macrophage M1 was negatively related with COL1A1 (p < 0.01) and LDLR (p < 0.01), while Macrophage M2 was positively related with COL1A1 (p < 0.01), TCF4 (p < 0.01), and H19 (p = 0.032). Two nomograms were conducted with favorable accuracies (area under curve of 1‐year survival: 0.935 and 0.877; 3‐year survival: 0.849 and 0.841; and 5‐year survival: 0.818 and 0.775, respectively). Conclusion The study constructed two nomograms suited for PRCC prognosis predicting. Moreover, we concluded that H19‐miR‐29c‐3p‐COL1A1 axis might promote the polarization of M2 macrophages and inhibit M1 macrophage activation through Wnt signaling pathway, collaborating to promote PRCC tumorigenesis and lead to poor overall survival of PRCC patients.