Methylation in MIRLET7A3 gene induces the expression of IGF-II and its mRNA binding proteins IGF2BP-2 and 3 in hepatocellular carcinoma
miR-let-7a is a tumor suppressor miRNA with reduced expression in most cancers. Methylation of MIRLET7A3 gene was reported to be the cause of this suppression in several cancers; however, it was not explicitly investigated in Hepatocellular Carcinoma (HCC). We aimed at investigating miR-let-7a expre...
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| Main Authors: | , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
24 January 2019
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| In: |
Frontiers in physiology
Year: 2019, Volume: 9 |
| ISSN: | 1664-042X |
| DOI: | 10.3389/fphys.2018.01918 |
| Online Access: | Verlag, Volltext: http://dx.doi.org/10.3389/fphys.2018.01918 Verlag, Volltext: https://www.frontiersin.org/articles/10.3389/fphys.2018.01918/full 
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| Author Notes: | Amr A. Waly, Nada El-Ekiaby, Reem A. Assal, Mohamed M. Abdelrahman, Karim A. Hosny, Hend M. El Tayebi, Gamal Esmat, Kai Breuhahn and Ahmed I. Abdelaziz |
| Summary: | miR-let-7a is a tumor suppressor miRNA with reduced expression in most cancers. Methylation of MIRLET7A3 gene was reported to be the cause of this suppression in several cancers; however, it was not explicitly investigated in Hepatocellular Carcinoma (HCC). We aimed at investigating miR-let-7a expression and molecular mode in HCC, identifying drug-targetable networks, which might be affected by its abundance. Our results illustrated a significant repression of miR-let-7a, which correlated with hypermethylation gene of origin MIRLRT7A3. This was further supported by the induction of miR-let-7a expression upon treatment of HCC cells with a DNA-methytransferase inhibitor. Using a computational approach, insulin-like growth factor (IGF)-II and IGF-2 mRNA binding proteins (IGF2BP)-2/-3 were identified as potential targets for miR-let-7a that was further confirmed experimentally. Indeed, miR-let-7a mimics diminished IGF-II as well as IGF2BP-2/-3 expression. In conclusion, this study suggests that DNA hypermethylation leads to epigenetic repression of miR-let-7a in HCC cells, which, induces the oncogenic IGF-signaling pathway. |
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| Item Description: | Gesehen am 01.03.2019 |
| Physical Description: | Online Resource |
| ISSN: | 1664-042X |
| DOI: | 10.3389/fphys.2018.01918 |