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Pak J Pharm Sci ; 34(3): 925-932, 2021 May.
Article in English | MEDLINE | ID: mdl-34602415

ABSTRACT

MicroRNA (miRNA)-26a is one of the tumor suppressor genes that has been down regulated during the development of hepatocellular carcinoma (HCC). This work was conducted to evaluate the possible preventive effect of exogenous miRNA-26a administration on diethylnitrosamine (DEN)-mediated HCC. Balb/C mice were intraperitoneally injected with saline (Normal group), DEN (HCC group) or miRNA-26a (HCC+miRNA-26a group). On week 8, 12, 16 and 20, the concentrations of alpha-fetoprotein (AFP), des-gamma carboxyprothrombin (DCP), the levels of helper T cells-associated cytokines, and the vascular endothelial growth factor (VEGF), were measured. Flow cytometry determined the frequencies of regulatory T (Treg) cells. The concentrations of AFP, DCP and VEGF, as well as the frequency of Treg cells showed significantly lower values following miRNA-26a administration than in HCC group. miRNA-26a administration has reduced the levels of IL (interleukin)-2 and TNF (tumor necrosis factor)-α, in contrast, IL-10 level was markedly elevated in comparison to HCC model at all experimental time points. The restore of miRNA-26a function significantly (P<0.001) down regulated the expression levels of survivin & caspase-3 compared to HCC group. The obtained data introduce an evidence for the suppressive impact of miRNA-26a on liver tumor formation and its possible manipulation as a therapeutic design for HCC.


Subject(s)
Carcinoma, Hepatocellular/metabolism , Liver Neoplasms, Experimental/metabolism , Liver Neoplasms/metabolism , Liver/drug effects , MicroRNAs/pharmacology , Alkylating Agents/toxicity , Animals , Apoptosis/drug effects , Biomarkers/metabolism , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/pathology , Caspase 3/drug effects , Caspase 3/metabolism , Cytokines/drug effects , Cytokines/metabolism , Diethylnitrosamine/toxicity , Interleukin-10/metabolism , Interleukin-2/metabolism , Liver/metabolism , Liver/pathology , Liver Neoplasms/genetics , Liver Neoplasms/pathology , Liver Neoplasms, Experimental/genetics , Liver Neoplasms, Experimental/pathology , Mice , Protein Precursors/drug effects , Protein Precursors/metabolism , Prothrombin/drug effects , Prothrombin/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Survivin/drug effects , Survivin/metabolism , T-Lymphocytes, Helper-Inducer/drug effects , T-Lymphocytes, Helper-Inducer/metabolism , Tumor Necrosis Factor-alpha/drug effects , Tumor Necrosis Factor-alpha/metabolism , Vascular Endothelial Growth Factor A/drug effects , Vascular Endothelial Growth Factor A/metabolism , alpha-Fetoproteins/drug effects , alpha-Fetoproteins/metabolism
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