In Silico and In Vivo Evaluation of microRNA-181c-5p’s Role in Hepatocellular Carcinoma
Hepatocellular carcinoma (HCC) is a fatal disease, accounting for 75–85% of primary liver cancers. The conclusive research on miR-181c-5p’s role in hepatocarcinogenesis, whether it has oncogenic effects or acts as a tumor repressor, is limited and fluctuating. Therefore, the current study aimed to e...
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MDPI AG
2022-12-01
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| Series: | Genes |
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| Online Access: | https://www.mdpi.com/2073-4425/13/12/2343 |
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| author | Omnia Nasser Abd ElAziz Asmaa M. Elfiky Mohamed A. Yassin Fatma El-Zahraa Abd El-Hakam Eman M. Saleh Mahmoud El-Hefnawi Rania Hassan Mohamed |
| author_facet | Omnia Nasser Abd ElAziz Asmaa M. Elfiky Mohamed A. Yassin Fatma El-Zahraa Abd El-Hakam Eman M. Saleh Mahmoud El-Hefnawi Rania Hassan Mohamed |
| author_sort | Omnia Nasser Abd ElAziz |
| collection | DOAJ |
| description | Hepatocellular carcinoma (HCC) is a fatal disease, accounting for 75–85% of primary liver cancers. The conclusive research on miR-181c-5p’s role in hepatocarcinogenesis, whether it has oncogenic effects or acts as a tumor repressor, is limited and fluctuating. Therefore, the current study aimed to elucidate the role of miR-181c-5p in HCC in silico and in vivo. The bioinformatics analysis of miR-181c-5p expression data in HCC using several databases strongly shed light on its involvement in HCC development, but also confirmed the fluctuating data around its role. miR-181c-5p was proven here to have an oncogenic role by increasing HepG2 cells’ viability as confirmed by MTT analysis. In addition, miR-181c-5p was upregulated in the HCC positive control group and progressed the HCC development and malignant features by its forced expression in an HCC mouse model by targeted delivery using a LA-PAMAM polyplex. This is indicated by the cancerous gross and histological features, and the significant increase in liver function biomarkers. The functional enrichment bioinformatics analyses of miR-181c-5p-downregulated targets in HCC indicated that miR-181c-5p targets were significantly enriched in multiple pathways and biological processes involved in HCC development. Fbxl3, an example for miR-181c-5p potential targets, downregulation and its correlation with miR-181c-5p were validated by qPCR. In conclusion, miR-181c-5p is upregulated in HCC and has an oncogenic role enhancing HCC progression. |
| first_indexed | 2024-03-09T16:28:48Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 2073-4425 |
| language | English |
| last_indexed | 2024-03-09T16:28:48Z |
| publishDate | 2022-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Genes |
| spelling | doaj.art-c58c594723224377b3def7585d73f2802023-11-24T15:05:20ZengMDPI AGGenes2073-44252022-12-011312234310.3390/genes13122343In Silico and In Vivo Evaluation of microRNA-181c-5p’s Role in Hepatocellular CarcinomaOmnia Nasser Abd ElAziz0Asmaa M. Elfiky1Mohamed A. Yassin2Fatma El-Zahraa Abd El-Hakam3Eman M. Saleh4Mahmoud El-Hefnawi5Rania Hassan Mohamed6Department of Biochemistry, Faculty of Science, Ain Shams University, Cairo 11566, EgyptNational Research Centre, Environmental and Occupational Medicine Department, Environmental Research Division, Cairo 12622, EgyptCenter of Excellence, National Research Centre, Advanced Materials and Nanotechnology Laboratory, Cairo 12622, EgyptDepartment of Pharmacology, Faculty of Medicine for Girls, Al-Azhar University, Cairo 11884, EgyptDepartment of Biochemistry, Faculty of Science, Ain Shams University, Cairo 11566, EgyptNational Research Centre, Biomedical Informatics and Cheminformatics Group, Informatics and Systems Department, Cairo 12622, EgyptDepartment of Biochemistry, Faculty of Science, Ain Shams University, Cairo 11566, EgyptHepatocellular carcinoma (HCC) is a fatal disease, accounting for 75–85% of primary liver cancers. The conclusive research on miR-181c-5p’s role in hepatocarcinogenesis, whether it has oncogenic effects or acts as a tumor repressor, is limited and fluctuating. Therefore, the current study aimed to elucidate the role of miR-181c-5p in HCC in silico and in vivo. The bioinformatics analysis of miR-181c-5p expression data in HCC using several databases strongly shed light on its involvement in HCC development, but also confirmed the fluctuating data around its role. miR-181c-5p was proven here to have an oncogenic role by increasing HepG2 cells’ viability as confirmed by MTT analysis. In addition, miR-181c-5p was upregulated in the HCC positive control group and progressed the HCC development and malignant features by its forced expression in an HCC mouse model by targeted delivery using a LA-PAMAM polyplex. This is indicated by the cancerous gross and histological features, and the significant increase in liver function biomarkers. The functional enrichment bioinformatics analyses of miR-181c-5p-downregulated targets in HCC indicated that miR-181c-5p targets were significantly enriched in multiple pathways and biological processes involved in HCC development. Fbxl3, an example for miR-181c-5p potential targets, downregulation and its correlation with miR-181c-5p were validated by qPCR. In conclusion, miR-181c-5p is upregulated in HCC and has an oncogenic role enhancing HCC progression.https://www.mdpi.com/2073-4425/13/12/2343hepatocellular carcinomanano-deliverymiR-181c-5pFbxl3oncogenic miRNA |
| spellingShingle | Omnia Nasser Abd ElAziz Asmaa M. Elfiky Mohamed A. Yassin Fatma El-Zahraa Abd El-Hakam Eman M. Saleh Mahmoud El-Hefnawi Rania Hassan Mohamed In Silico and In Vivo Evaluation of microRNA-181c-5p’s Role in Hepatocellular Carcinoma Genes hepatocellular carcinoma nano-delivery miR-181c-5p Fbxl3 oncogenic miRNA |
| title | In Silico and In Vivo Evaluation of microRNA-181c-5p’s Role in Hepatocellular Carcinoma |
| title_full | In Silico and In Vivo Evaluation of microRNA-181c-5p’s Role in Hepatocellular Carcinoma |
| title_fullStr | In Silico and In Vivo Evaluation of microRNA-181c-5p’s Role in Hepatocellular Carcinoma |
| title_full_unstemmed | In Silico and In Vivo Evaluation of microRNA-181c-5p’s Role in Hepatocellular Carcinoma |
| title_short | In Silico and In Vivo Evaluation of microRNA-181c-5p’s Role in Hepatocellular Carcinoma |
| title_sort | in silico and in vivo evaluation of microrna 181c 5p s role in hepatocellular carcinoma |
| topic | hepatocellular carcinoma nano-delivery miR-181c-5p Fbxl3 oncogenic miRNA |
| url | https://www.mdpi.com/2073-4425/13/12/2343 |
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