BackgroundComplex molecular events lead to development and progression of liver cirrhosis to HCC. Differentially expressed nuclear membrane associated proteins are responsible for the functional and structural alteration during the progression from cirrhosis to carcinoma. Although alterations/ post translational modifications in protein expression have been extensively quantified, complementary analysis of nuclear membrane proteome changes have been limited. Deciphering the molecular mechanism that differentiate between normal and disease state may lead to identification of biomarkers for carcinoma.ResultsMany proteins displayed differential expression when nuclear membrane proteome of hepatocellular carcinoma (HCC), fibrotic liver, and HepG2 cell line were assessed using 2-DE and ESI-Q-TOF MS/MS. From the down regulated set in HCC, we have identified for the first time a 15 KDa cytochrome b5A (CYB5A), ATP synthase subunit delta (ATPD) and Hemoglobin subunit beta (HBB) with 11, 5 and 22 peptide matches respectively. Furthermore, nitrosylation studies with S-nitrosocysteine followed by immunoblotting with anti SNO-cysteine demonstrated a novel and biologically relevant post translational modification of thiols of CYB5A in HCC specimens only. Immunofluorescence images demonstrated increased protein S-nitrosylation signals in the tumor cells and fibrotic region of HCC tissues. The two other nuclear membrane proteins which were only found to be nitrosylated in case of HCC were up regulated ATP synthase subunit beta (ATPB) and down regulated HBB. The decrease in expression of CYB5A in HCC suggests their possible role in disease progression. Further insight of the functional association of the identified proteins was obtained through KEGG/ REACTOME pathway analysis databases. String 8.3 interaction network shows strong interactions with proteins at high confidence score, which is helpful in characterization of functional abnormalities that may be a causative factor of liver pathology.ConclusionThese findings may have broader implications for understanding the mechanism of development of carcinoma. However, large scale studies will be required for further verification of their critical role in development and progression of HCC.
Objective: To determine the frequency of Klebsiella pneumoniae Carbapenemase (bla KPC ) and New Delhi Metallo-Beta-Lactamase (bla NDM ) resistant genes among clinical isolates of Enterobacterales in a set of Karachi population.
Identification of biomarker will obligate a substantial influence on various cancer management and treatment. We hypothesize that genetic/proteomic and epigenetic studies should be uncovering modifications which may be independently or jointly affect the expression of the genes that are involved in the progression of liver cancer (LC). For this purpose, we examined the effect of expressional changes of DNMTs on HCV infected LC of different genotypes. We found that both mRNA and protein expression levels of DNMT1, 3a, and 3b were upregulated in genotype 1b and 3a HCV infected patients as compared to control. However, DNMT3b mRNA levels did not change in genotypes 2a, 3, and 4, but were upregulated at the protein level by genotype 1b, 2a, and 3a. Furthermore, no significant changes were observed for DNMTs investigated in sample expressing the genotypes 5 and 6. Our findings suggest that HCV at least in part by altering DNMTs expression may play a significant role in HCC progression.
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