Inhibition of protein kinase C isozymes causes immune profile alteration and possibly decreased tumorigenesis in bladder cancer.

Protein kinase C (PRKC) isozymes activate many signaling pathways and promote tumorigenesis, which can be confirmed by masking the kinase activity. In the present study, the kinase activity of PRKC ε and ζ isozymes was masked by siRNA in bladder cancer, and the consequent gene profile was evaluated. Here, we show that the commonly dysregulated genes affected by both the isozymes were the chemokines (CXCL8 & CXCL10), adhesion molecules (ICAM1, SPP1, MMP3, VEGFA) and mutated isoform of TP53. As these same genes were upregulated in bladder cancer patients, the activity of the kinase in downregulating them is confirmed. These genes are associated with regulating the tumor microenvironment, proliferation and differentiation of cancer cells and poor prognosis. The effect of kinase masking in downregulating these genes in bladder cancer indicates the benefits PRKC inhibitors may have in managing these patients.

Scouting for common genes in the heterogenous hypoxic tumor microenvironment and their validation in glioblastoma.

Investigating the therapeutic and prognostic potential of genes in the heterogeneous hypoxic niche of glioblastoma. We have analyzed RNA expression of U87MG cells cultured in hypoxia compared to normoxia. Common differentially expressed genes (DEGs) from GSE45301 and GSE18494 and their functional enrichment was performed using MetaScape and PANTHER. Hub genes and their ontology were identified using MCode cytoHubba and ClueGO and validated with GlioVis, Oncomine, HPA and PrognoScan. Using the GEO2R analysis of GSE45301 and GSE18494 datasets, we have found a total of 246 common DEGs (180 upregulated and 66 downregulated) and identified 2 significant modules involved in ribosome biogenesis and TNF signaling. Meta-analysis of key genes of each module in cytoHubba identified 17 hub genes (ATF3, BYSL, DUSP1, EGFR, JUN, ETS1, LYAR, NIP7, NOLC1, NOP2, NOP56, PNO1, RRS1, TNFAIP3, TNFRSF1B, UTP15, VEGFA). Of the 17 hub genes, ATF3, BYSL, EGFR, JUN, NIP7, NOLC1, PNO1, RRS1, TNFAIP3 and VEGFA were identified as hypoxia signatures associated with poor prognosis in Glioma. Ribosome biogenesis emerged as a vital contender of possible therapeutic potential with BYSL, NIP7, NOLC1, PNO1 and RRS1 showing prognostic value. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13205-021-02987-2.