Abstract
High mobility group A (HMGA) proteins are oncofoetal chromatin architectural factors that are widely involved in regulating gene expression. These proteins are unique, because they are highly expressed in embryonic and cancer cells, where they play a relevant role in cell proliferation, stemness, and the acquisition of aggressive tumour traits, i.e., motility, invasiveness, and metastatic properties. The HMGA protein expression levels and activities are controlled by a connected set of events at the transcriptional, post-transcriptional, and post-translational levels. In fact, microRNA (miRNA)-mediated RNA stability is the most-studied mechanism of HMGA protein expression modulation. In this review, we contribute to a comprehensive overview of HMGA-targeting miRNAs; we provide detailed information regarding HMGA gene structural organization and a comprehensive evaluation and description of HMGA-targeting miRNAs, while focusing on those that are widely involved in HMGA regulation; and, we aim to offer insights into HMGA-miRNA mutual cross-talk from a functional and cancer-related perspective, highlighting possible clinical implications.
Highlights
We contribute to a comprehensive overview of High mobility group A (HMGA)-targeting miRNAs; we provide detailed information regarding HMGA gene structural organization and a comprehensive evaluation and description of HMGA-targeting miRNAs, while focusing on those that are widely involved in HMGA regulation; and, we aim to offer insights into HMGA-miRNA mutual cross-talk from a functional and cancer-related perspective, highlighting possible clinical implications
The high mobility group A (HMGA) family is a family of architectural nuclear proteins that are involved in the modulation of chromatin structure and regulation of gene expression
The targeting of both mRNAs by multiple miRNAs suggests a degree of interdependence between the two proteins; in most research that is related to HMGA proteins, only one protein (i.e., HMGA1 or HMGA2) is studied without considering the possible interdependence with the other
Summary
The high mobility group A (HMGA) family is a family of architectural nuclear proteins that are involved in the modulation of chromatin structure and regulation of gene expression. The family comprises three main members: HMGA1a and HMGA1b, which are derived from the alternative splicing of the HMGA1 gene, and HMGA2, which is derived from a different— related—gene [1,2] These small proteins (approximately 12 kDa) contain three DNA-binding domains, the so-called “AT-hooks”, which allow for them to bind short A/T-rich sequences through the DNA minor groove, and a highly acidic C-terminal tail [3]. Post-transcriptional regulation is a key process that regulates gene expression, and it is often altered in cancer cells [42,43] Both the 5 untranslated region (5’UTR) and 3 UTR can contribute to this process, the 3 UTR in particular is more often a target of microRNAs (miRNAs), which are the most important factors that are involved in this type of regulation.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
