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MiR-590-3p suppresses cellular migration and clonogenicity and epithelial to mesenchymal transition in the HepG2 cell line by targeting MDM2 and SETD7
MiRNAs signature is dysregulated in various types of cancer, and several miRNAs have a dual regulatory role either as tumor suppressors or oncogenes depending on the tissue context. MiR-590-3p has been previously identified to regulate different cancers, yet its role in hepatocellular carcinoma (HCC...
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AUC Knowledge Fountain
2020
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| Summary: | MiRNAs signature is dysregulated in various types of cancer, and several miRNAs have a dual regulatory role either as tumor suppressors or oncogenes depending on the tissue context. MiR-590-3p has been previously identified to regulate different cancers, yet its role in hepatocellular carcinoma (HCC) is still elusive with contradictory findings. In our study, the expression levels of miR-590-3p, as well as its function in HCC, were examined in two different HCC cell lines: HepG2 and SNU449 that represent an early and advanced stage of HCC, respectively. Real-time Polymerase Chain Reaction analysis revealed that miR-590-3p is downregulated in HCC and its levels are more decreased as HCC advances to a more malignant state. Functional analysis was performed by ectopically overexpressing and inhibiting miR-590-3p using miRNA mimics and inhibitors in HepG2 and SNU449 cells. Using Condition-Specific miRNA Targets (CSmiRTar) database to predict mir-590-3p targets, MDM2, and SETD7 were identified. A validation of the two targets was demonstrated through an established negative correlation between their mRNA levels and miR-590-3p level in both cell lines. Further validation of the two genes was represented in the decreased mRNA expression upon overexpressing miR-590-3p. Furthermore, miR-590-3p overexpression was able to decrease epithelial to mesenchymal transition by directly reducing the mRNA level of the mesenchymal marker N-cadherin. MiR-590-3p also suppressed cell migration and reduced clonogenicity in the HepG2 cell line. Interestingly, real-time PCR and western blotting analyses revealed stabilization of p53 mRNA and protein levels as a result of miR-590-3p transfection in both HepG2 and SNU449 cells, which could be mainly attributed to a unique dual regulation event from both MDM2 and SETD7 on p53 that eventually led to a stable p53 expression. Finally, our results confirm a tumor-suppressive role of miR-590-3p in HCC through the regulation of both MDM2 and SETD7. |
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