Possible Role of microRNA-122 in Modulating Multidrug Resistance of Hepatocellular Carcinoma |
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| Authors: | Shaymaa M M Yahya Shadia A Fathy Zakaria A El-Khayat Safinaz E El-Toukhy Ahmed R Hamed Marwa G A Hegazy Heba K Nabih |
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| Institution: | 1.Hormones Department,National Research Centre,Dokki, Giza,Egypt;2.Biochemistry Department,Ain Shams University,Cairo,Egypt;3.Medical Biochemistry Department,National Research Centre,Cairo,Egypt;4.Pharmaceutical Research Group,Center of Excellence for Advanced Sciences and Phytochemistry Department National Research Centre,Dokki, Giza,Egypt |
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| Abstract: | Hepatocellular carcinoma (HCC) is a hypervascular primary liver cancer characterized by rapid progression, besides, resistance to traditional chemotherapeutic agents. It has been shown that microRNAs play critical roles in regulation of tumor cell sensitivity to drugs through modulating the expression of genes involved in drug transport. The present study investigated whether restoration of miR-122 in HCC cells could alter the cell cycle distribution and the expression of multidrug resistance (MDR)-related genes (ABCB1, ABCC1, ABCG2 and ABCF2). After overexpression of miR-122 in HepG2 cells treated or untreated with doxorubicin doses, total RNAs and protein extracts were isolated for application of QRT-PCR and western blotting techniques. Moreover, cell cycle distribution was monitored by flow cytometry. Our results revealed that, the over expression of miR-122 in HepG2 cells treated or untreated with doxorubicin could modulate the sensitivity of cells to chemotherapeutic drug through downregulation of MDR-related genes, ABCB1 and ABCF2. Interpretation of cell cycle distribution revealed that, the anti-proliferative effect of miR-122 is associated with the accumulation of cells in G0/G1 phase. Moreover, treatment with miR-122 and doxorubicin resulted in high percentage of HCC cells in G0/G1 phase. Taken together, our findings revealed that, overexpression of miR-122 inhibited HCC cell growth by inducing cell cycle arrest and this arrest is associated with down-regulation of MDR-related genes. |
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