Downregulation of miR-23a and miR-24 in human hepatocellular carcinoma cells by Sorafenib via transforming growth factor-beta 1 in a SMAD dependent manner | ||||
| Journal of Bioscience and Applied Research | ||||
| Article 7, Volume 5, Issue 3, September 2019, Page 340-351 PDF (558.2 K) | ||||
| Document Type: Original Article | ||||
| DOI: 10.21608/jbaar.2019.147398 | ||||
 View on SCiNiTO | ||||
| Authors | ||||
Eman G. Ayad1; Mohga S. Abdulla  1; Hayat M. Sharada1; Abdel Hady A. Abdel Wahab2; Abeer M. Ashmawy2
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| 1Department of Chemistry, Faculty of Science, Helwan University, Egypt | ||||
| 2Departments of Cancer Biology, National Cancer Institute, Cairo University, Egypt | ||||
| Abstract | ||||
| MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression through post-transcriptional interactions with mRNA. MiRNAs have recently been considered as key regulators of various cancers including liver cancer. Sorafenib is one of the antitumor drugs for the treatment of advanced hepatocellular carcinoma. It acts as a multikinase inhibitor suppressing cell proliferation and angiogenesis. This study tries to investigate a potential microRNA-based mechanism of action of the drug by studying the effect of sorafenib on miR-23a and miR-24 levels in HCC cell lines HepG2 /Huh7 and revealing the possible drug mechanism against these oncogenic mi-RNAS in this study cell viability of cultured HepG2 /Huh7 after treatment with sorafenib were evaluated using Sulphorhodamine-B (SRB) assay, cell cycle, and apoptosis estimated by flow cytometry assay. The caspase-3 level was determined using the ELISA assay. Moreover, miR-23a and miR-24 expression levels were analyzed by qPCR. Finally, TGF-β levels and phosphorylated smad2, 3 were examined after treatment with sorafenib using ELISA and western blotting. Our data confirmed the Sorafenib inhibition of cell growth in both cell lines which was accompanied by a significant increase in cell apoptosis and cell cycle arrest. Cells treated with sorafenib showed a significant decrease in miR-23a and miR-24 levels in both cell lines. Interestingly, the change in these oncogenic miRNAs was accompanied by a significant decrease of (TGF-β1) and phosphorylated smad2, 3 protein levels. Our study suggested that inhibition of the tgf beta pathway in smad dependent manner could be the way characteristic of sorafenib to inhibit the oncogenic miR-23a and miR-24 levels in HCC. | ||||
| Keywords | ||||
| hepatocellular carcinoma cells; microRNAs; miR-23a; miR-24; sorafenib; TGF-β1 | ||||
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