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Methylation Dynamics of RASSF1A and Its Impact on Cancer

Department of Surgical Sciences, Dentistry, Gynecology and Pediatrics, Section of Surgery, University of Verona, 37134 Verona, Italy
Department of Diagnostics and Public Health, Section of Anatomic Pathology, University of Verona, 37134 Verona, Italy
Department of Medicine, Section of Pharmacology, University of Verona, 37134 Verona, Italy
Department of Biomedical Sciences, University of Ngaoundere, Ngaoundere 454, Cameroon
Department of Biosciences, COMT-Centre for Molecular and Translational Oncology, University of Parma, 43124 Parma, Italy
Author to whom correspondence should be addressed.
Cancers 2019, 11(7), 959;
Received: 12 June 2019 / Revised: 3 July 2019 / Accepted: 8 July 2019 / Published: 9 July 2019
PDF [2599 KB, uploaded 18 July 2019]


5-methyl cytosine (5mC) is a key epigenetic mark entwined with gene expression and the specification of cellular phenotypes. Its distribution around gene promoters sets a barrier for transcriptional enhancers or inhibitor proteins binding to their target sequences. As a result, an additional level of regulation is added to the signals that organize the access to the chromatin and its structural components. The tumor suppressor gene RASSF1A is a microtubule-associated and multitasking scaffold protein communicating with the RAS pathway, estrogen receptor signaling, and Hippo pathway. RASSF1A action stimulates mitotic arrest, DNA repair and apoptosis, and controls the cell cycle and cell migration. De novo methylation of the RASSF1A promoter has received much attention due to its increased frequency in most cancer types. RASSF1A methylation is preceded by histones modifications and could represent an early molecular event in cell transformation. Accordingly, RASSF1A methylation is proposed as an epigenetic candidate marker in many cancer types, even though an inverse correlation of methylation and expression remains to be fully ascertained. Some findings indicate that the epigenetic abrogation of RASSF1A can promote the alternative expression of the putative oncogenic isoform RASSF1C. Understanding the complexity and significance of RASSF1A methylation is instrumental for a more accurate determination of its biological and clinical role. The review covers the molecular events implicated in RASSF1A methylation and gene silencing and provides a deeper view into the significance of the RASSF1A methylation patterns in a number of gastrointestinal cancer types. View Full-Text
Keywords: RASSF1; RASSF1A; DNA methylation; grastrointestinal cancers; biomarker RASSF1; RASSF1A; DNA methylation; grastrointestinal cancers; biomarker

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Malpeli, G.; Innamorati, G.; Decimo, I.; Bencivenga, M.; Nwabo Kamdje, A.H.; Perris, R.; Bassi, C. Methylation Dynamics of RASSF1A and Its Impact on Cancer. Cancers 2019, 11, 959.

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