Emerging roles for HMGA2 in colorectal cancer

Abstract

HMGA2 (High Mobility Group AT-hook 2) has been reported to promote colorectal cancer (CRC) development by regulating the transcription of target genes. It participates in nearly all aspects of cellular processes, including cell transformation, proliferation, apoptosis, senescence, metastasis, epithelial-to-mesenchymal transition (EMT), DNA repair and stem cell self-renewal. In the past decades, a group of downstream targets and binding partners have been identified in a wide range of cancers. Our findings of HMGA2 as a key factor in the MDM2/p53, IL11/STAT3 and Wnt/β-catenin signaling pathways prompt us to summarize current advances in the functional and molecular basis of HMGA2 in CRC. In this review, we address the roles of HMGA2 in the oncogenic networks of CRC based on recent advances. We review its aberrant expression, explore underlying mechanisms, discuss its pro-tumorigenic effects, and highlight promising small-molecule inhibitors based on targeting HMGA2 here. However, the understanding of HMGA2 in CRC progression is still elusive, thus we also discuss the future perspectives in this review. Collectively, this review provides novel insights into the oncogenic properties of HMGA2, which has potential implications in the diagnosis and treatment of CRC.

Keywords: HMGA2; colorectal cancer; inhibitors; ncRNAs; signaling pathways.

Fig. 1

Scheme of HMGA2-mediated signaling pathways and functions in CRC. HMGA2 directly activated the transcription of IL11, Slug, FN1 and Dvl2 in CRC. HMGA2 directly repressed the transcription of miR-194 in CRC. HMGA2 directly interacted with p53 and MDM2, thereby increasing MDM2-mediated p53 ubiquitination and subsequently decreasing its expression. Upstream factors accounted for dysregulation of HMGA2 in CRC, including KLK6, ZNF382 and high glucose.

Fig. 2

Scheme of ncRNAs and inhibitors that regulate HMGA2 in CRC.