Immunology Research Center, Tabriz University of Medical Sciences, Tabriz 51656-65811, Iran.
Student Research Committee, Tabriz University of Medical Sciences, Tabriz 51656-65811, Iran.
Genes (Basel). 2021 Feb 13;12(2):269. doi: 10.3390/genes12020269.
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.
高迁移率族蛋白 2（HMGA2）通过与富含 AT 的 DNA 区域结合来调节基因表达。与其他 DNA 结构蛋白类似，HMGA2 在胚胎发生过程中的胚胎干细胞中高度表达，而在发育的后期阶段和成年期其表达更为有限。重要的是，HMGA2 在几乎所有人类恶性肿瘤中重新表达，通过多种机制促进肿瘤发生。HMGA2 通过促进细胞周期进入和抑制细胞凋亡来增加癌细胞的增殖。此外，HMGA2 通过激活 MAPK/ERK、TGFβ/Smad、PI3K/AKT/mTOR、NFkB 和 STAT3 通路的信号转导，影响不同的 DNA 修复机制并促进上皮间质转化。此外，HMGA2 支持癌症干细胞表型，并使癌细胞对化疗药物产生耐药性。在这篇综述中，我们讨论了 HMGA2 在不同类型癌症中的这些致癌作用，并提出 HMGA2 可能用于癌症的诊断、预后和治疗目的。
