Abstract
Hepatocellular carcinoma (HCC) is the third leading malignancy worldwide, causing mortality in children and adults. AEG-1 is functioned as a scaffold protein for the proper assembly of RNA-induced silencing complex (RISC) to optimize or increase its activity. The increased activity of oncogenic miRNAs leads to the degradation of target tumor suppressor genes. miR-221 is an oncogenic miRNA, that plays a seminal role in carcinogenesis regulation of HCC. However, the molecular mechanism and biological functions of the miR-221/AEG-1 axis have not been investigated extensively in HCC. Here, the expression of miR-221/AEG-1 and their target/associate genes was analyzed by qRT-PCR and Western blot. The role of the miR-221/AEG-1 axis in HCC was evaluated by proliferation assay, migration assay, invasion assay, and flow cytometry analysis. The expression level of miR-221 decreased in AEG-1 siRNA transfected HCC cells. On the other hand, there were no significant expression changes of AEG-1 in miR-221 mimic and miR-221 inhibitor transfected HCC cells and inhibition of miR-221/AEG-1 axis decreased cell proliferation, invasion, migration, and angiogenesis and induced apoptosis, cell cycle arrest by upregulating p57, p53, PTEN, and RB and downregulating LSF, MMP9, OPN, Bcl-2, PI3K, AKT, and LC3A in HCC cells. Furthermore, these findings suggest that the miR-221/AEG-1 axis plays a seminal oncogenic role by modulating PTEN/PI3K/AKT signaling pathway in HCC. In conclusion, the miR-221/AEG-1 axis may serve as a potential target for therapeutics, diagnostics, and prognostics of HCC.
Highlights
Hepatocellular carcinoma (HCC) is the fifth common malignancy and observed third leading cancer-caused death with a limited prediction [1]
Our study shows that knockdown of miR-221 and Astrocyte elevated gene-1 (AEG-1) inhibits cell proliferation, angiogenesis, and induced apoptosis in sub-G0-G1 and G2-M phase arrested in miR-221 inhibitor or AEG-1 small interfering RNA (siRNA) transfected HCC cells
We showed that miR-221 and AEG-1expressionisupregulated by and associated with HCC tumorigenesis
Summary
Hepatocellular carcinoma (HCC) is the fifth common malignancy and observed third leading cancer-caused death with a limited prediction [1]. Hepatitis B virus (HBV) and hepatitis C virus (HCV) are the major risk factor for human HCC. Most of HCC patients suffer from HBV infections, approximately 50–80% of cases, and 10 to 25% of HCV [3]. NAFLD is the major cause of liver damage that leads to liver cirrhosis and HCC [4]. NAFLD is the major non-viral risk factor for developing HCC worldwide. In India, 9–32% of cases affected by NAFLD are associated with HCC [5]. Recent studies showed that chemotherapy is the best treatment for HCC [6]. A better approach to improve the molecular biological studies and targeted therapy for the regulatory networks of cell proliferation, apoptosis, and angiogenesis progression could be more effective in the treatment of HCC
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