High mobility group AT-hook 2 (HMGA2) (HMGA2)

High mobility group AT-hook 2 (HMGA2) is a non-histone architectural transcription factor that plays a critical role in chromatin remodeling and the regulation of gene expression [1, 16]. Primarily expressed during embryonic development and largely absent in adult tissues, HMGA2 is frequently re-expressed in a wide range of human malignancies, where it functions as an oncogene [4, 8, 18]. It promotes tumorigenesis by influencing multiple biological processes, including the cell cycle, apoptosis, and epithelial-mesenchymal transition (EMT) [4, 9, 21]. Notably, HMGA2 is a key regulator of DNA repair pathways, such as base excision repair (BER) and nucleotide excision repair (NER), often by interacting with proteins like PARP1 or regulating the transcription of repair genes like ERCC1 [2, 7, 13]. This involvement in DNA repair contributes to genomic stability in cancer cells and mediates resistance to DNA-damaging chemotherapies and PARP inhibitors [5, 13, 15]. Consequently, HMGA2 is considered a promising therapeutic target and a valuable prognostic biomarker in oncology [10, 12, 17, 22].

Other names

High mobility group protein HMGI-C [16, 19]HMGI-C [16]HMGIC [16]BABL [16]LIPO [16]High mobility group AT-hook protein 2 [19]

HMGA2 acts as an architectural transcription factor that binds to AT-rich DNA sequences, altering chromatin structure to facilitate or inhibit the recruitment of DNA repair proteins such as PARP1 and ERCC1 [1, 7, 13]. Experimental strategies to target this pathway include the use of DNA aptamers to block protein-DNA interactions and RNA interference (siRNA/shRNA) to silence gene expression, thereby sensitizing cancer cells to DNA-damaging agents and PARP inhibitors [10, 12, 17].