Abstract
The high mobility group protein 2 (HMGA2) regulates gene expression by binding to AT-rich regions of DNA. Akin to other DNA architectural proteins, HMGA2 is highly expressed in embryonic stem cells during embryogenesis, while its expression is more limited at later stages of development and in adulthood. Importantly, HMGA2 is re-expressed in nearly all human malignancies, where it promotes tumorigenesis by multiple mechanisms. HMGA2 increases cancer cell proliferation by promoting cell cycle entry and inhibition of apoptosis. In addition, HMGA2 influences different DNA repair mechanisms and promotes epithelial-to-mesenchymal transition by activating signaling via the MAPK/ERK, TGFβ/Smad, PI3K/AKT/mTOR, NFkB, and STAT3 pathways. Moreover, HMGA2 supports a cancer stem cell phenotype and renders cancer cells resistant to chemotherapeutic agents. In this review, we discuss these oncogenic roles of HMGA2 in different types of cancers and propose that HMGA2 may be used for cancer diagnostic, prognostic, and therapeutic purposes.
Highlights
High mobility group (HMG) proteins are nonhistone, chromatin-associated molecules involved in maintenance and functional regulation of DNA, including the processes of replication, recombination, transcription, and DNA repair [1]
We showed that miR-330 targets High Mobility Group Protein 2 (HMGA2) and stable induction of miR-330 expression inhibits Snail1 and increases E-cadherin expression in breast cancer cells [28]
The authors showed that the mRNA expression level of Inner Mitochondrial Membrane Peptidase Subunit 2 (IMP2) increased nearly two-fold in HMGA2-induced cells compared to control cells [172]
Summary
High mobility group (HMG) proteins are nonhistone, chromatin-associated molecules involved in maintenance and functional regulation of DNA, including the processes of replication, recombination, transcription, and DNA repair [1]. The biological activities of HMG proteins are regulated through epigenetic mechanisms, which affect their interactions with DNA and other transcription factors. Akin to the other protein family members, HMGA2 regulates gene expression by binding to the DNA minor groove and chromatin management [11]. The HMGA2 AT-binding domains are each comprised of nine amino acids, including the invariable repeat Arg-Gly-Arg-Pro [12] During transcription, these domains can bind to BB--sshhaappeeddDDNNAAaannddcoconnvveretrittiftrofrmomdidsoisrodredrerdetdotoordoerdreedrecdoncfoonrfmoramtioantiso.nBsa. sBedasoendtohne nthuemnbuemr abnerdalnodcaltoiocnatioofnthoef tAheT-AriTc-hribchinbdiinndginsigtessi,teHs,MHGMAG2Aa2ffeacfftsectthsethceoncfoonrfmoramtioantioonf DofNDANiAn isnevservaelrawl awyas.ysB.yBiynifnlufleunecnincgingthtehestsrturcutcutruereofofDDNNAA, ,ititccaanncchhaannggeeiittss effect on transcription by enhancing or suppressing the activities of nnumerous genes, affecting various biological processes [6]. These include the let-7 family [27], miR-330 [28], miR-98-5p [29], miR-33-5p [30], miR-34a-5p [31], miR-497 [32], and miR-491 [33]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
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 call
