Methylation in MIRLET7A3 Gene Induces the Expression of IGF-II and Its mRNA Binding Proteins IGF2BP-2 and 3 in Hepatocellular Carcinoma
Amr A. Waly,Nada El-Ekiaby,R.A. Assal,Mohamed M. Abdelrahman,Karim Hosny,Hend M. El Tayebi,Gamal Esmat,Kai Breuhahn,Ahmed Ihab Abdelaziz +8 more
TLDR
This study suggests that DNA hypermethylation leads to epigenetic repression of miR-let-7a in HCC cells, which induces the oncogenic IGF-signaling pathway.Abstract:
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 of its gene of origin MIRLRT7A3. This was further supported by the induction of miR-let-7a expression upon treatment of HCC cells with a DNA-methyltransferase 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. Direct binding of miR-let-7a to each respective transcript was confirmed using a luciferase reporter assay. 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.read more
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CRD-BP mediates stabillization of βTrCP1 and c-mys mRNA in response to β-catenin signalling
Felicite K. Noubissi,Irina Elcheva,Neehar Bhatia,A. Shakoori,Andrei V. Ougolkov,J. Lui,Toshinari Minamoto,Jeffrey Ross,Serge Y. Fuchs,Vladimir S. Spiegelman +9 more
TL;DR: The authors showed that β-catenin stabilizes the mRNA encoding the F-box protein βTrCP1, and identified the RNA-binding protein CRD-BP (coding region determinant-binding proteins) as a previously unknown target of β-Catenin/Tcf transcription factor.
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MicroRNA: A signature for cancer progression.
Bashdar Mahmud Hussen,Hazha Jamal Hidayat,Abbas Salihi,Dana Khdr Sabir,Mohammad Taheri,Soudeh Ghafouri-Fard +5 more
TL;DR: In this article, the authors discuss several circulating miRNA signatures, their expression profiles in different types of cancer and their impacts on cellular processes, and use them to categorize genes that can affect oncogenic pathways in cancer.
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The role of IGF2BP2, an m6A reader gene, in human metabolic diseases and cancers
TL;DR: The human insulin-like growth factor 2 mRNA binding proteins 2 (IGF2BP2/IMP2) is an RNA-binding protein that regulates multiple biological processes as discussed by the authors.
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N 6 ‐methyladenosine (m 6 A) RNA modification in human cancer
TL;DR: This review aimed to summarize the current knowledge on the potential significance and molecular mechanisms of m6A RNA modification in the initiation and progression of cancer.
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The IGF2BP family of RNA binding proteins links epitranscriptomics to cancer.
Deepthi Ramesh-Kumar,Sonia Guil +1 more
TL;DR: In this paper , the regulatory roles of IGF2BP proteins and their molecular role as m6A modification readers to the cellular phenotype are summarized and a comprehensive insight into the IGF 2BP function is provided.
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