Wang Xin, Wang Jian, Wu Jingjing
Department of Pathology & Pathophysiology, Department of Colorectal Surgery of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
Department of Colorectal Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
Transl Oncol. 2021 Jan;14(1):100894. doi: 10.1016/j.tranon.2020.100894. Epub 2020 Oct 14.
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.
据报道，高迁移率族AT钩蛋白2（HMGA2）可通过调控靶基因转录促进结直肠癌（CRC）发展。它参与细胞过程的几乎所有方面，包括细胞转化、增殖、凋亡、衰老、转移、上皮-间质转化（EMT）、DNA修复和干细胞自我更新。在过去几十年中，已在多种癌症中鉴定出一组HMGA2的下游靶点和结合伙伴。我们发现HMGA2是MDM2/p53、IL11/STAT3和Wnt/β-连环蛋白信号通路中的关键因子，这促使我们总结HMGA2在结直肠癌中功能和分子基础的当前进展。在本综述中，我们基于最近的进展阐述HMGA2在结直肠癌致癌网络中的作用。我们回顾其异常表达，探究潜在机制，讨论其促肿瘤作用，并在此重点介绍基于靶向HMGA2的有前景的小分子抑制剂。然而，对HMGA2在结直肠癌进展中的理解仍不明确，因此我们在本综述中也讨论了未来展望。总体而言，本综述为HMGA2的致癌特性提供了新见解，这对结直肠癌的诊断和治疗具有潜在意义。
