MicroRNA-26a systemic administration attenuates tumor formation in hepatocellular carcinoma mouse model

Theodor Bilharz Research Institute

Bibliographic Information

Authors: Badr A.M.; El-Ahwany E.; Goda L.; Nagy F.; Helal N.; Deeb S.E.

Journal: Pakistan Journal of Pharmaceutical Sciences

Publisher: Pakistan Journal of Pharmaceutical Sciences

Publication Date: 1 May 2021

Volume / Issue: Volume 34 / Issue 3

Pages: 925–932

ISSN: 1011601X

DOI: 10.36721/PJPS.2021.34.3.REG.925-932.1

Scopus: View on Scopus

PubMed: 34602415

Document Type: Article

Access: All Open Access; Gold Open Access

Authors and Affiliations

Badr A.M., Zoology Department, Faculty of Science, Cairo University, Giza, Egypt; El-Ahwany E., Immunology Department, Theodor Bilharz Research Institute (TBRI), Giza, Egypt; Goda L., Zoology Department, Faculty of Science, Cairo University, Giza, Egypt; Nagy F., Immunology Department, Theodor Bilharz Research Institute (TBRI), Giza, Egypt; Helal N., Pathology Department, Theodor Bilharz Research Institute (TBRI), Giza, Egypt; Deeb S.E., Zoology Department, Faculty of Science, Cairo University, Giza, Egypt

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. © 2021 Pakistan Journal of Pharmaceutical Sciences. All rights reserved.

Keywords

Caspase-3; Cytokines; DEN; HCC; MiRNA-26a; Regulatory T cells; Survivin; Tumor markers; VEGF; Alkylating Agents; alpha-Fetoproteins; Animals; Apoptosis; Biomarkers; Carcinoma, Hepatocellular; Caspase 3; Diethylnitrosamine; Interleukin-10; Interleukin-2; Liver; Liver Neoplasms; Liver Neoplasms, Experimental; Mice; MicroRNAs; Protein Precursors; Prothrombin; Reverse Transcriptase Polymerase Chain Reaction; T-Lymphocytes, Helper-Inducer; Tumor Necrosis Factor-alpha; Vascular Endothelial Growth Factor A; alpha fetoprotein; baculoviral IAP repeat containing protein 5; decarboxyprothrombin; interleukin 10; interleukin 2; microRNA 26a; tumor necrosis factor; vasculotropin; alkylating agent; biological marker; Casp3 protein, mouse; cytokine; IL10 protein, mouse; microRNA; Mirn26 microRNA, mouse; protein precursor; Tnf protein, mouse; vasculotropin A; animal cell; animal experiment; animal model; Article; Bagg albino mouse; controlled study; down regulation; enzyme linked immunosorbent assay; flow cytometry; histology; liver carcinogenesis; liver cell carcinoma; male; mouse; mouse model; nonhuman; protein blood level; protein expression level; regulatory T lymphocyte; animal; drug effect; experimental liver neoplasm; genetics; helper cell; liver tumor; metabolism; pathology; reverse transcription polymerase chain reaction

Citation Information

Scopus Citations: 3

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